Mahmood Reza Amiry-Moghaddam

• Doncel, Beatriz Escobar; Zhang, Xiaoyi; Ljøstad, Åsne; Puebla, Mario Fernández de la; Shreyas, Rao & Fjeldstad, Synnøve Algrøy [Show all 11 contributors for this article] (2026). Two-photon in vivo imaging reveals cell type-specific mitophagy dynamic changes in mouse somatosensory cortex during aging. npj Aging. 12. doi: 10.1038/s41514-026-00414-5. Full text in Research Archive Show summary

  Mitochondrial homeostasis is majorly maintained through mitochondrial autophagy (mitophagy). Recent research highlights the region- and cell type-specific nature of mitophagy during brain aging; however, these dynamics have largely remained unexplored in living brains. To address this gap, we conducted two-photon mt-Keima imaging in somatosensory cortical neurons and astrocytes in behaving male mice across two age groups, including 2–3-month-old (early-aged) and 18–20-month-old (old-aged) mice. We show reduced mitophagy in both cell types during aging, and we consistently found a higher level of mitophagy in astrocytes compared to neurons at the same age, in both age groups. Pharmacological augmentation of NAD+, a pivotal metabolite that induces mitophagy but normally declines in the aging brain, increased cellular mitophagy in both neurons and astrocytes in old-aged male mice at the dose and method of administration tested. Collectively, our data support an age-dependent reduction of mitophagy in neurons and astrocytes, at least in mouse somatosensory cortex, while NAD+ repletion offsets such reduction.

• Frey, Mina Martine; Izadpanah, Negar Zohoorian; Skauli, Nadia; Ottersen, Ole Petter & Amiry-Moghaddam, Mahmood (2025). Are diurnal variations in glymphatic clearance driven by circadian regulation of Aquaporin-4 expression? Fluids and Barriers of the CNS. 22(1), p. 1–11. doi: 10.1186/s12987-025-00676-3. Full text in Research Archive Show summary

  Aquaporin-4 (AQP4) is a key astrocytic water channel protein predominantly localized to perivascular endfeet, where it is believed to play a crucial role in brain fluid homeostasis and glymphatic waste clearance. Previous studies have suggested that the perivascular expression of AQP4 is regulated by circadian rhythms and peaks during the sleep phase, potentially influencing glymphatic function. However, direct evidence supporting circadian regulation of AQP4 remains limited. Here, we investigated AQP4 expression and perivascular distribution in the hippocampus and neocortex of mice at mid rest (day) and mid active phase (night). We employed quantitative immunogold electron microscopy (EM), in addition to immunofluorescence confocal microscopy, Western blotting, and qPCR to assess AQP4 localization and expression at the mRNA and protein levels. Our findings revealed no significant differences in AQP4 perivascular localization, total protein levels, or mRNA expression between day and night. Furthermore, the expression of key dystrophin-associated protein complex (DAPC) components, which anchor AQP4 to astrocytic endfeet, also remained largely unchanged. These results challenge the hypothesis that AQP4 localization is regulated by circadian rhythms and suggest that previously reported circadian differences in glymphatic function are mediated by factors other than AQP4 expression. This study highlights the need for further research into the mechanisms governing glymphatic function.

• Maré, Sofia W. de; Steffen, Jonas Hyld; Missel, Julie W.; Laursen, Amalie Gerdt; Gotfryd, Kamil & Fisher, Zoë [Show all 9 contributors for this article] (2025). Crystallization of Human Aquaglyceroporins for Neutron Diffraction Studies. ACS Omega. 10(8), p. 7806–7812. doi: 10.1021/acsomega.4c08284. Full text in Research Archive Show summary

  Aquaglyceroporins are channels that facilitate the flux of glycerol and water across lipid bilayers. Although structural information is available for several aquaglyceroporins, the details of how water and glycerol selectivity are maintained and how protons are excluded remain elusive. An approach to obtaining data on the hydrogen atom positions is to apply neutron macromolecular crystallography. Here, we present strategies to obtain large crystals suitable for neutron diffraction experiments by assessing a range of different methods, including new procedures for protein purification and crystallization. By applying long incubation times, macroseeding, and/or optimization of detergents, millimeter-sized crystals with different morphologies were obtained, and their diffraction quality was assessed by exposure to X-rays. The data presented here lay the foundation for continued crystallization efforts targeting aquaporins and other membrane proteins for neutron diffraction experiments.

• Bojarskaite, Laura; Nafari, Sahar; Ravnanger, Anne Katrine; Frey, Mina Martine; Skauli, Nadia & Åbjørsbråten, Knut Sindre [Show all 13 contributors for this article] (2024). Role of aquaporin-4 polarization in extracellular solute clearance. Fluids and Barriers of the CNS. 21(1). doi: 10.1186/s12987-024-00527-7. Full text in Research Archive Show summary

  Waste from the brain has been shown to be cleared via the perivascular spaces through the so-called glymphatic system. According to this model the cerebrospinal fluid (CSF) enters the brain in perivascular spaces of arteries, crosses the astrocyte endfoot layer, flows through the parenchyma collecting waste that is subsequently drained along veins. Glymphatic clearance is dependent on astrocytic aquaporin-4 (AQP4) water channels that are highly enriched in the endfeet. Even though the polarized expression of AQP4 in endfeet is thought to be of crucial importance for glymphatic CSF influx, its role in extracellular solute clearance has only been evaluated using non-quantitative fluorescence measurements. Here we have quantitatively evaluated clearance of intrastriatally infused small and large radioactively labeled solutes in mice lacking AQP4 (Aqp4–/–) or lacking the endfoot pool of AQP4 (Snta1–/–). We confirm that Aqp4–/– mice show reduced clearance of both small and large extracellular solutes. Moreover, we find that the Snta1–/– mice have reduced clearance only for the 500 kDa [3H]dextran, but not 0.18 kDa [3H]mannitol suggesting that polarization of AQP4 to the endfeet is primarily important for clearance of large, but not small molecules. Lastly, we observed that clearance of 500 kDa [3H]dextran increased with age in adult mice. Based on our quantitative measurements, we confirm that presence of AQP4 is important for clearance of extracellular solutes, while the perivascular AQP4 localization seems to have a greater impact on clearance of large versus small molecules.

• Holl, Daniel; Hau, Wing Fung; Julien, Anais; Banitalebi, Shervin; Kalkitsas, Jannis & Savant, Soniya [Show all 12 contributors for this article] (2024). Distinct origin and region-dependent contribution of stromal fibroblasts to fibrosis following traumatic injury in mice. Nature Neuroscience. ISSN 1097-6256. 27, p. 1285–1298. doi: 10.1038/s41593-024-01678-4. Full text in Research Archive Show summary

  Fibrotic scar tissue formation occurs in humans and mice. The fibrotic scar impairs tissue regeneration and functional recovery. However, the origin of scar-forming fibroblasts is unclear. Here, we show that stromal fibroblasts forming the fibrotic scar derive from two populations of perivascular cells after spinal cord injury (SCI) in adult mice of both sexes. We anatomically and transcriptionally identify the two cell populations as pericytes and perivascular fibroblasts. Fibroblasts and pericytes are enriched in the white and gray matter regions of the spinal cord, respectively. Both cell populations are recruited in response to SCI and inflammation. However, their contribution to fibrotic scar tissue depends on the location of the lesion. Upon injury, pericytes and perivascular fibroblasts become activated and transcriptionally converge on the generation of stromal myofibroblasts. Our results show that pericytes and perivascular fibroblasts contribute to the fibrotic scar in a region-dependent manner.

• Skauli, Nadia; Izadpanah, Negar Zohoorian; Banitalebi, Shervin; Geiseler, Samuel Jakob; Salameh, Maher & Shreyas, Rao [Show all 9 contributors for this article] (2024). Aquaporin-4 deletion leads to reduced infarct volume and increased peri-infarct astrocyte reactivity in a mouse model of cortical stroke. Journal of Physiology. ISSN 0022-3751. 602(13), p. 3151–3168. doi: 10.1113/JP284099. Full text in Research Archive Show summary

  Aquaporin-4 (AQP4) is the main water channel in brain and is enriched in perivascular astrocyte processes abutting brain microvessels. There is a rich literature on the role of AQP4 in experimental stroke. While its role in oedema formation following middle cerebral artery occlusion (MCAO) has been studied extensively, its specific impact on infarct volume remains unclear. This study investigated the effects of total and partial AQP4 deletion on infarct volume in mice subjected to distal medial cerebral artery (dMCAO) occlusion. Compared to MCAO, this model induces smaller infarcts confined to neocortex, and less oedema. We show that AQP4 deletion significantly reduced infarct volume as assessed 1 week after dMCAO, suggesting that the role of AQP4 in stroke goes beyond its effect on oedema formation and dissolution. The reduction in infarct volume was associated with increased astrocyte reactivity in the peri-infarct areas. No significant differences were observed in the number of microglia among the genotypes. These findings provide new insights in the role of AQP4 in ischaemic injury indicating that AQP4 affects both infarct volume and astrocyte reactivity in the peri-infarct zone.

• Huang, Peng; Åbacka, Hannah; Varela, Daniel; Venskutonytė, Raminta; Happonen, Lotta & Bogan, Jonathan S. [Show all 10 contributors for this article] (2023). The intracellular helical bundle of human glucose transporter GLUT4 is important for complex formation with ASPL. FEBS Open Bio. 13(11), p. 2094–2107. doi: 10.1002/2211-5463.13709. Full text in Research Archive Show summary

  Glucose transporters (GLUTs) are responsible for transporting hexose molecules across cellular membranes. In adipocytes, insulin stimulates glucose uptake by redistributing GLUT4 to the plasma membrane. In unstimulated adipose‐like mouse cell lines, GLUT4 is known to be retained intracellularly by binding to TUG protein, while upon insulin stimulation, GLUT4 dissociates from TUG. Here, we report that the TUG homolog in human, ASPL, exerts similar properties, i.e., forms a complex with GLUT4. We describe the structural details of complex formation by combining biochemical assays with cross‐linking mass spectrometry and computational modeling. Combined, the data suggest that the intracellular domain of GLUT4 binds to the helical lariat of ASPL and contributes to the regulation of GLUT4 trafficking by cooperative binding.

• Ohtonen, Sohvi; Giudice, Luca; Jäntti, Henna; Fazaludeen, Mohammad Feroze; Shakirzyanova, Anastasia & Gómez-Budia, Mireia [Show all 17 contributors for this article] (2023). Human iPSC-derived microglia carrying the LRRK2-G2019S mutation show a Parkinson’s disease related transcriptional profile and function. Scientific Reports. 13. doi: 10.1038/s41598-023-49294-9. Full text in Research Archive Show summary

  Abstract LRRK2-G2019S is one of the most common Parkinson’s disease (PD)-associated mutations and has been shown to alter microglial functionality. However, the impact of LRRK2-G2019S on transcriptional profile of human induced pluripotent stem cell-derived microglia-like cells (iMGLs) and how it corresponds to microglia in idiopathic PD brain is not known. Here we demonstrate that LRRK2-G2019S carrying iMGL recapitulate aspects of the transcriptional signature of human idiopathic PD midbrain microglia. LRRK2-G2019S induced subtle and donor-dependent alterations in iMGL mitochondrial respiration, phagocytosis and cytokine secretion. Investigation of microglial transcriptional state in the midbrains of PD patients revealed a subset of microglia with a transcriptional overlap between the in vitro PD-iMGL and human midbrain PD microglia. We conclude that LRRK2-G2019S iMGL serve as a model to study PD-related effects in human microglia.

• Tan, Mandy; Chin, Jiah Shin; Madden, Leigh Edward; Knutsen, Maja Fjellstad; Ugland, Hege & Karlsson, Magdalena Kauczynska [Show all 8 contributors for this article] (2023). Oxygenated Hydrogel Promotes Re-Epithelialization and Reduces Inflammation in a Perturbed Wound Model in Rat. Journal of Pharmaceutical Sciences. ISSN 0022-3549. doi: 10.1016/j.xphs.2023.10.011. Full text in Research Archive
• Zahl, Soulmaz; Skauli, Nadia; Stahl, Katja; Prydz, Agnete; Frey, Mina Martine & Dissen, Erik [Show all 8 contributors for this article] (2023). Aquaporin-9 in the Brain Inflammatory Response: Evidence from Mice Injected with the Parkinsonogenic Toxin MPP⁺. Biomolecules. 13(4). doi: 10.3390/biom13040588. Full text in Research Archive Show summary

  More than 20 years have passed since the first demonstration of Aquaporin-9 (AQP9) in the brain. Yet its precise localization and function in brain tissue remain unresolved. In peripheral tissues, AQP9 is expressed in leukocytes where it is involved in systemic inflammation processes. In this study, we hypothesized that AQP9 plays a proinflammatory role in the brain, analogous to its role in the periphery. We also explored whether Aqp9 is expressed in microglial cells, which would be supportive of this hypothesis. Our results show that targeted deletion of Aqp9 significantly suppressed the inflammatory response to the parkinsonian toxin 1-methyl-4-phenylpyridinium (MPP+). This toxin induces a strong inflammatory response in brain. After intrastriatal injections of MPP+, the increase in transcript levels of proinflammatory genes was less pronounced in AQP9−/− mice compared with wild-type controls. Further, in isolated cell subsets, validated by flow cytometry we demonstrated that Aqp9 transcripts are expressed in microglial cells, albeit at lower concentrations than in astrocytes. The present analysis provides novel insight into the role of AQP9 in the brain and opens new avenues for research in the field of neuroinflammation and chronic neurodegenerative disease.

• Banitalebi, Shervin; Skauli, Nadia; Geiseler, Samuel; Ottersen, Ole Petter & Amiry-Moghaddam, Mahmood (2022). Disassembly and Mislocalization of AQP4 in Incipient Scar Formation after Experimental Stroke. International Journal of Molecular Sciences. ISSN 1661-6596. 23(3). doi: 10.3390/ijms23031117. Full text in Research Archive Show summary

  There is an urgent need to better understand the mechanisms involved in scar formation in the brain. It is well known that astrocytes are critically engaged in this process. Here, we analyze incipient scar formation one week after a discrete ischemic insult to the cerebral cortex. We show that the infarct border zone is characterized by pronounced changes in the organization and subcellular localization of the major astrocytic protein AQP4. Specifically, there is a loss of AQP4 from astrocytic endfoot membranes that anchor astrocytes to pericapillary basal laminae and a disassembly of the supramolecular AQP4 complexes that normally abound in these membranes. This disassembly may be mechanistically coupled to a downregulation of the newly discovered AQP4 isoform AQP4ex. AQP4 has adhesive properties and is assumed to facilitate astrocyte mobility by permitting rapid volume changes at the leading edges of migrating astrocytes. Thus, the present findings provide new insight in the molecular basis of incipient scar formation.

• Skauli, Nadia; Savchenko, Ekaterina; Ottersen, Ole Petter; Roybon, Laurent & Amiry-Moghaddam, Mahmood (2022). Canonical Bone Morphogenetic Protein Signaling Regulates Expression of Aquaporin-4 and Its Anchoring Complex in Mouse Astrocytes. Frontiers in Cellular Neuroscience. 16. doi: 10.3389/fncel.2022.878154. Full text in Research Archive Show summary

  Aquaporin-4 (AQP4) is the predominant water channel in the brain; it is enriched in astrocytic foot processes abutting vessels where it is anchored through an interaction with the dystrophin-associated protein (DAP) complex. Enhanced expression with concomitant mislocalization of AQP4 along astrocyte plasma membranes is a hallmark of several neurological conditions. Thus, there is an urgent need to identify which signaling pathways dictate AQP4 microdistribution. Here we show that canonical bone morphogenetic proteins (BMPs), particularly BMP2 and 4, upregulate AQP4 expression in astrocytes and dysregulate the associated DAP complex by differentially affecting its individual members. We further demonstrate the presence of BMP receptors and Smad1/5/9 pathway activation in BMP treated astrocytes. Our analysis of adult mouse brain reveals BMP2 and 4 in neurons and in a subclass of endothelial cells and activated Smad1/5/9 in astrocytes. We conclude that the canonical BMP-signaling pathway might be responsible for regulating the expression of AQP4 and of DAP complex proteins that govern the subcellular compartmentation of this aquaporin.

• Rao, Shreyas Balachandra; Skauli, Nadia; Jovanovic, Nenad; Katoozi, Shirin; Frigeri, Antonio & Froehner, Stanley C. [Show all 9 contributors for this article] (2021). Orchestrating aquaporin-4 and connexin-43 expression in brain: Differential roles of α1- and β1-syntrophin. Biochimica et Biophysica Acta - Biomembranes. ISSN 0005-2736. 1863(8), p. 1–14. doi: 10.1016/j.bbamem.2021.183616. Full text in Research Archive
• Dias, David O.; Kalkitsas, Jannis; Kelahmetoglu, Yildiz; Estrada, Cynthia P.; Tatarishvili, Jemal & Holl, Daniel [Show all 16 contributors for this article] (2021). Pericyte-derived fibrotic scarring is conserved across diverse central nervous system lesions. Nature Communications. 12. doi: 10.1038/s41467-021-25585-5. Full text in Research Archive Show summary

  Abstract Fibrotic scar tissue limits central nervous system regeneration in adult mammals. The extent of fibrotic tissue generation and distribution of stromal cells across different lesions in the brain and spinal cord has not been systematically investigated in mice and humans. Furthermore, it is unknown whether scar-forming stromal cells have the same origin throughout the central nervous system and in different types of lesions. In the current study, we compared fibrotic scarring in human pathological tissue and corresponding mouse models of penetrating and non-penetrating spinal cord injury, traumatic brain injury, ischemic stroke, multiple sclerosis and glioblastoma. We show that the extent and distribution of stromal cells are specific to the type of lesion and, in most cases, similar between mice and humans. Employing in vivo lineage tracing, we report that in all mouse models that develop fibrotic tissue, the primary source of scar-forming fibroblasts is a discrete subset of perivascular cells, termed type A pericytes. Perivascular cells with a type A pericyte marker profile also exist in the human brain and spinal cord. We uncover type A pericyte-derived fibrosis as a conserved mechanism that may be explored as a therapeutic target to improve recovery after central nervous system lesions.

• Prydz, Agnete; Stahl, Katja; Rahmani, Soulmaz; Skauli, Nadia; Skare, Øivind & Ottersen, Ole Petter [Show all 7 contributors for this article] (2020). Pro-inflammatory role of AQP4 in mice subjected to intrastriatal injections of the Parkinsonogenic toxin MPP. Cells. 9:2418(11). doi: 10.3390/cells9112418. Full text in Research Archive Show summary

  Aquaporin-4 (AQP4) is critically involved in brain water and volume homeostasis and has been implicated in a wide range of pathological conditions. Notably, evidence has been accrued to suggest that AQP4 plays a proinflammatory role by promoting release of astrocytic cytokines that activate microglia and other astrocytes. Neuroinflammation is a hallmark of Parkinson's disease (PD), and we have previously shown that astrocytes in substantia nigra (SN) are enriched in AQP4 relative to cortical astrocytes, and that their complement of AQP4 is further increased following treatment with the parkinsonogenic toxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). Here, we investigated the effect of Aqp4 deletion on microglial activation in mice subjected to unilateral intrastriatal injection of 1-methyl-4-phenylpyridinium (MPP+, the toxic metabolite of MPTP). Our results show that MPP+ injections lead to a pronounced increase in the expression level of microglial activating genes in the ventral mesencephalon of wild type (WT) mice, but not Aqp4-/- mice. We also show, in WT mice, that MPP+ injections cause an upregulation of nigral AQP4 and swelling of astrocytic endfeet. These findings are consistent with the idea that AQP4 plays a pro-inflammatory role in Parkinson's disease, secondary to the dysregulation of astrocytic volume homeostasis.

• Bellis, Manuela de; Cibelli, Antonio; Mola, Maria Grazia; Pisani, Francesco; Barile, Barbara & Mastrodonato, Maria [Show all 12 contributors for this article] (2020). Orthogonal arrays of particle assembly are essential for normal aquaporin-4 expression level in the brain. Glia. ISSN 0894-1491. doi: 10.1002/glia.23909. Full text in Research Archive Show summary

  Astrocyte endfeet are endowed with aquaporin‐4 (AQP4)‐based assemblies called orthogonal arrays of particles (OAPs) whose function is still unclear. To investigate the function of OAPs and of AQP4 tetramers, we have generated a novel “OAP‐null” mouse model selectively lacking the OAP forming M23‐AQP4 isoform. We demonstrated that AQP4 transcript levels were not reduced by using qPCR. Blue native (BN)/SDS‐PAGE and Western blot performed on OAP‐null brain and primary astrocyte cultures showed the complete depletion of AQP4 assemblies, the selective expression of M1‐AQP4‐based tetramers, and a substantial reduction in AQP4 total expression level. Fluorescence quenching and super‐resolution microscopy experiments showed that AQP4 tetramers were functionally expressed in astrocyte plasma membrane and their dimensions were reduced compared to wild‐type assemblies. Finally, as shown by light and electron microscopy, OAP depletion resulted in a massive reduction in AQP4 expression and a loss of perivascular AQP4 staining at astrocyte endfeet, with only sparse labeling throughout the brain areas analyzed. Our study relies on the unique property of AQP4 to form OAPs, using a novel OAP‐null mouse model for the first time, to show that (a) AQP4 assembly is essential for normal AQP4 expression level in the brain and (b) most of AQP4 is organized into OAPs under physiological conditions. Therefore, AQP4 tetramers cannot be used by astrocytes as an alternative to OAPs without affecting AQP4 expression levels, which is important in the physiological and pathological conditions in which OAP aggregation/disaggregation dynamics have been implicated.

• Palazzo, Claudia; Abbrescia, Pasqua; Valente, Onofrio; Nicchia, Grazia Paola; Banitalebi, Shervin & Amiry-Moghaddam, Mahmood [Show all 8 contributors for this article] (2020). Tissue Distribution of the Readthrough Isoform of AQP4 Reveals a Dual Role of AQP4ex Limited. International Journal of Molecular Sciences. ISSN 1661-6596. 21(4), p. 1–14. doi: 10.3390/ijms21041531. Full text in Research Archive Show summary

  Translational readthrough (TRT) of aquaporin-4 (AQP4) has remarkably expanded the importance of this new post-transcriptional mechanism, as well as the regulation potential of AQP4. The TRT isoform of AQP4, named AQP4ex, is central for both AQP4 polarization and water channel activity in the central nervous system (CNS). Here we evaluate the relevance of the TRT mechanism by analyzing whether AQP4ex is also expressed in peripheral tissues and whether the expression of AQP4ex is necessary for its polarized expression as it occurs in perivascular astrocyte processes. To this purpose, AQP4ex null mice were used, and analysis was performed by immunolocalization and immunoblot. The results demonstrate that AQP4ex is expressed in kidney, stomach, trachea and skeletal muscle with the same localization pattern as the canonical AQP4 isoforms. AQP4ex protein levels vary from 6% to about 13% of the total AQP4 protein levels in peripheral tissues. Immunogold electron microscopy experiments demonstrated the localization of AQP4ex at the astrocytic endfeet, and experiments conducted on AQP4ex null mice CNS confirmed that the expression of AQP4ex is necessary for anchoring of the perivascular AQP4. Without the readthrough isoform, AQP4 assemblies are mis-localized, being uniformly distributed on the astrocyte processes facing the neuropile. No alteration of AQP4 polarization was found in AQP4ex null kidney, stomach, trachea or skeletal muscle, suggesting that AQP4ex does not have a role for proper membrane localization of AQP4 in peripheral tissues. We conclude that a dual role for AQP4ex is limited to the CNS.

• Hoddevik, Eystein Hellstrøm; Rao, Shreyas Balachandra; Rahmani, Soulmaz; Boldt, Henning Bunsow; Ottersen, Ole Petter & Amiry-Moghaddam, Mahmood (2020). Organisation of extracellular matrix proteins laminin and agrin in pericapillary basal laminae in mouse brain. Brain Structure and Function. ISSN 1863-2653. 225, p. 805–816. doi: 10.1007/s00429-020-02036-3. Full text in Research Archive Show summary

  Abstract Evidence suggests that extracellular matrix molecules of perivascular basal laminae help orchestrate the molecular assemblies at the gliovascular interface. Specifically, laminin and agrin are thought to tether the dystrophin-associated protein (DAP) complex to the astrocytic basal lamina. This complex includes α-syntrophin (α-Syn), which is believed to anchor aquaporin-4 (AQP4) to astrocytic endfoot membrane domains. We have previously shown that the size of the perivascular AQP4 pool differs considerably between brain regions in an α-Syn-dependent manner. Also, both AQP4 and α-Syn occur at higher densities in endfoot membrane domains facing pericytes than in endfoot membrane domains facing endothelial cells. The heterogeneous distribution of AQP4 at the regional and capillary level has been attributed to a direct interaction between AQP4 and α-Syn. This would be challenged (1) if the microdistributions of laminin and agrin fail to align with those of DAP and AQP4 and (2) if targeted deletion of α-Syn leads to a loss of laminin and/or agrin. Here, we provide the first detailed and quantitative analysis of laminin and agrin in brain basal laminae of mice. We show that the microdistributions of these molecules vary in a fashion that is well aligned with the previously reported microdistribution of AQP4. We also demonstrate that the expression patterns of laminin and agrin are insensitive to targeted deletion of α-Syn, suggesting that α-Syn deletion affects AQP4 directly and not indirectly via laminin or agrin. These data fill remaining voids in the current model of how key molecules are assembled and tethered at the gliovascular interface.

• Katoozi, Shirin; Shreyas, Rao; Skauli, Nadia; Froehner, Stanley C.; Ottersen, Ole Petter & Adams, Marv [Show all 7 contributors for this article] (2020). Functional specialization of retinal Müller cell endfeet depends on an interplay between two syntrophin isoforms. Molecular Brain. 13. doi: 10.1186/s13041-020-00581-w. Full text in Research Archive Show summary

  Retinal Müller cells are highly polarized macroglial cells with accumulation of the aquaporin-4 (AQP4) water channel and the inwardly rectifying potassium channel Kir4.1 at specialized endfoot membrane domains abutting microvessels and corpus vitreum. Proper water and potassium homeostasis in retina depends on these membrane specializations. Here we show that targeted deletion of β1-syntrophin leads to a partial loss of AQP4 from perivascular Müller cell endfeet and that a concomitant deletion of both α1- and β1-syntrophin causes a near complete loss of AQP4 from both perivascular and subvitreal endfoot membranes. α1-syntrophin is normally very weakly expressed in Müller cell endfeet but β1-syntrophin knockout mice display an increased amount of α1-syntrophin at these sites. We suggest that upregulation of perivascular α1-syntrophin restricts the effect of β1-syntrophin deletion. The present findings indicate that β1-syntrophin plays an important role in maintaining the functional polarity of Müller cells and that α1-syntrophin can partially substitute for β1-syntrophin in AQP4 anchoring. Functional polarization of Müller cells thus depends on an interplay between two syntrophin isoforms.

• Katoozi, Shirin; Skauli, Nadia; Rahmani, Soulmaz; Deshpande, Tushar; Ezan, Pascal & Palazzo, Claudia [Show all 11 contributors for this article] (2020). Uncoupling of the Astrocyte Syncytium Differentially Affects AQP4 Isoforms. Cells. doi: 10.3390/cells9020382. Full text in Research Archive Show summary

  The water channel protein aquaporin-4 (AQP4) and the gap junction forming proteins connexin-43 (Cx43) and connexin-30 (Cx30) are astrocytic proteins critically involved in brain water and ion homeostasis. While AQP4 is mainly involved in water flux across the astrocytic endfeet membranes, astrocytic gap junctions provide syncytial coupling allowing intercellular exchange of water, ions, and other molecules. We have previously shown that mice with targeted deletion of Aqp4 display enhanced gap junctional coupling between astrocytes. Here, we investigate whether uncoupling of the astrocytic syncytium by deletion of the astrocytic connexins Cx43 and Cx30 affects AQP4 membrane localization and expression. By using quantitative immunogold cytochemistry, we show that deletion of astrocytic connexins leads to a substantial reduction of perivascular AQP4, concomitant with a down-regulation of total AQP4 protein and mRNA. Isoform expression analysis shows that while the level of the predominant AQP4 M23 isoform is reduced in Cx43/Cx30 double deficient hippocampal astrocytes, the levels of M1, and the alternative translation AQP4ex isoform protein levels are increased. These findings reveal a complex interdependence between AQP4 and connexins, which are both significantly involved in homeostatic functions and astrogliopathologies.

• Vatnehol, Svein Are Sirirud; Hol, Per Kristian; Bjørnerud, Atle; Amiry-Moghaddam, Mahmood; Haglerød, Camilla & Storås, Tryggve (2020). Effect of drinking oxygenated water assessed by in vivo MRI relaxometry. Journal of Magnetic Resonance Imaging. ISSN 1053-1807. 52(3), p. 720–728. doi: 10.1002/jmri.27104. Full text in Research Archive Show summary

  Grant Support This project was funded by the Research Council of Norway. Background Oxygen uptake through the gastrointestinal tract after oral administration of oxygenated water in humans is not well studied and is debated in the literature. Due to the paramagnetic properties of oxygen and deoxyhemoglobin, MRI as a technique might be able to detect changes in relaxometry values caused by increased oxygen levels in the blood. Purpose To assess whether oxygen dissolved in water is absorbed from the gastrointestinal tract and transported into the bloodstream after oral administration. Study Type A randomized, double‐blinded, placebo‐controlled crossover trial. Population/Subjects Thirty healthy male volunteers age 20–35. Field Strength/Sequence 3T/Modified Look–Locker inversion recovery (MOLLI) T1‐mapping and multi fast field echo (mFFE) T2*‐mapping. Assessment Each volunteer was scanned in two separate sessions. T1 and T2* maps were acquired repeatedly covering the hepatic portal vein (HPV) and vena cava inferior (VCI, control vein) before and after intake of oxygenated or control water. Assessments were done by placing a region of interest in the HPV and VCI. Statistical Test A mixed linear model was performed to the compare control vs. oxygen group. Results Drinking caused a mean 1.6% 95% CI (1.1–2.0% P < 0.001) increase in T1 of HPV blood and water oxygenation attributed another 0.70% 95% confidence interval (CI) (0.07–1.3% P = 0.028) increase. Oxygenation did not change T1 in VCI blood. Mean T2* increased 9.6% 95% CI (1.7–17.5% P = 0.017) after ingestion of oxygenated water and 1.2% 95% CI (−4.3–6.8% P = 0.661) after ingestion of control water. The corresponding changes in VCI blood were not significant. Data Conclusion Ingestion of water caused changes in T1 and T2* of HPV blood compatible with dilution due to water absorption. The effects were enhanced by oxygen. Assessment of oxygen enrichment of HPV blood was not possible due to the dilution effect. Level of Evidence 2 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2020;52:720–728.

• Rao, Shreyas Balachandra; Katoozi, Shirin; Skauli, Nadia; Froehner, Stanley C.; Ottersen, Ole Petter & Adams, Marvin E. [Show all 7 contributors for this article] (2019). Targeted deletion of β1-syntrophin causes a loss of Kir 4.1 from Müller cell endfeet in mouse retina. Glia. ISSN 0894-1491. 67(6), p. 1138–1149. doi: 10.1002/glia.23600. Full text in Research Archive Show summary

  Proper function of the retina depends heavily on a specialized form of retinal glia called Müller cells. These cells carry out important homeostatic functions that are contingent on their polarized nature. Specifically, the Müller cell endfeet that contact retinal microvessels and the corpus vitreum show a tenfold higher concentration of the inwardly rectifying potassium channel Kir4.1 than other Müller cell plasma membrane domains. This highly selective enrichment of Kir4.1 allows K+ to be siphoned through endfoot membranes in a special form of spatial buffering. Here, we show that Kir4.1 is enriched in endfoot membranes through an interaction with β1‐syntrophin. Targeted disruption of this syntrophin caused a loss of Kir4.1 from Müller cell endfeet without affecting the total level of Kir4.1 expression in the retina. Targeted disruption of α1‐syntrophin had no effect on Kir4.1 localization. Our findings show that the Kir4.1 aggregation that forms the basis for K+ siphoning depends on a specific syntrophin isoform that colocalizes with Kir4.1 in Müller endfoot membranes.

• Vatnehol, Svein Are Sirirud; Hol, Per Kristian; Bjørnerud, Atle; Amiry-Moghaddam, Mahmood; Haglerød, Camilla Margrete & Storås, Tryggve (2019). Precision of T1-relaxation time measurements in the hepatic portal vein: influence of measurement technique and sequence parameters. Magnetic Resonance Materials in Physics, Biology and Medicine. ISSN 0968-5243. 32(3), p. 359–368. doi: 10.1007/s10334-018-00731-1. Full text in Research Archive
• Formaggio, Francesco; Saracino, Emanuela; Mola, Maria Grazia; Rao, Shreyas Balachandra; Amiry-Moghaddam, Mahmood & Muccini, Michele [Show all 10 contributors for this article] (2019). LRRC8A is essential for swelling-activated chloride current and for regulatory volume decrease in astrocytes. The FASEB Journal. ISSN 0892-6638. 33(1), p. 101–113. doi: 10.1096/fj.201701397RR. Full text in Research Archive
• Vatnehol, Svein Are Sirirud; Hol, Per Kristian; Bjørnerud, Atle; Amiry-Moghaddam, Mahmood; Haglerød, Camilla Margrete & Storås, Tryggve (2019). Determination of oxygen r1 at 3 Tesla using samples with a concentration range of dissolved oxygen. Magnetic Resonance Materials in Physics, Biology and Medicine. ISSN 0968-5243. p. 1–7. doi: 10.1007/s10334-019-00783-x. Full text in Research Archive Show summary

  Objective To investigate the sensitivity of modified Look–Locker inversion recovery (MOLLI) to measure changes in dissolved oxygen (DO) concentrations in water samples and to calculate sequence-specific relaxivity (r1m) and limit of detection (LOD). Materials and methods Ten water samples with a range of DO concentrations were scanned at 3 T using two variations of MOLLI schemes. Using linear regression the r1 of DO was estimated from the measured DO concentrations and T1 relaxation rates (R1). The results were combined with previously reported values on in vivo stability measures of the MOLLI sequences and used to estimate a LOD. Results DO concentrations ranged from 0.5 to 21.6 mg L−1. A linear correlation between DO and R1 was obtained with both MOLLI sequences, with an average correlation coefficient (R2) 0.9 and an average estimated r1 (r^1) of 4.45 × 10−3 s−1 mg−1 L. Estimated LOD was ≈ 10 mg L−1. Conclusion MOLLI T1-mapping sequences may be used for detecting dissolved oxygen in vivo at 3 T with an r^1 in the range 4.18–4.8 × 10−3 s−1 mg−1 L and a corresponding LOD for dissolved oxygen of approximately 10 mg L−1. MOLLI-based T1 mapping may be a useful non-invasive tool for quantification of in vivo changes of DO concentration during oxygen challenges.

• Amiry-Moghaddam, Mahmood (2019). AQP4 and the fate of gliomas. Cancer Research. ISSN 0008-5472. 79(11), p. 2810–2811. doi: 10.1158/0008-5472.CAN-19-1185. Full text in Research Archive Show summary

  High-grade glioma is the most common primary brain cancer type and is characterized by invasive and fast growth. In a previous issue of Cancer Research, Simone and colleagues show that the two isoforms of the aquaporin-4 (AQP4) water channel may determine the fate of gliomas. Glioma cell lines expressing the M23-AQP4 isoform, which forms large aggregates of orthogonal arrays of particles, shrink and undergo apoptosis, whereas cell lines expressing the tetramer-forming M1-AQP4 isoform display higher activity of matrix metalloproteinases, making them more invasive. This study provides new insight on the role of AQP4 isoforms in the biology of gliomas.

• Stahl, Katja; Rahmani, Soulmaz; Prydz, Agnete; Skauli, Nadia; MacAulay, Nanna & Mylonakou, Maria-Niki [Show all 13 contributors for this article] (2018). Targeted deletion of the aquaglyceroporin AQP9 is protective in a mouse model of Parkinson's disease. PLOS ONE. 13(3). doi: 10.1371/journal.pone.0194896. Full text in Research Archive Show summary

  More than 90% of the cases of Parkinson’s disease have unknown etiology. Gradual loss of dopaminergic neurons of substantia nigra is the main cause of morbidity in this disease. External factors such as environmental toxins are believed to play a role in the cell loss, although the cause of the selective vulnerability of dopaminergic neurons remains unknown. We have previously shown that aquaglyceroporin AQP9 is expressed in dopaminergic neurons and astrocytes of rodent brain. AQP9 is permeable to a broad spectrum of substrates including purines, pyrimidines, and lactate, in addition to water and glycerol. Here we test our hypothesis that AQP9 serves as an influx route for exogenous toxins and, hence, may contribute to the selective vulnerability of nigral dopaminergic (tyrosine hydroxylase-positive) neurons. Using Xenopus oocytes injected with Aqp9 cRNA, we show that AQP9 is permeable to the parkinsonogenic toxin 1-methyl-4-phenylpyridinium (MPP+). Stable expression of AQP9 in HEK cells increases their vulnerability to MPP+ and to arsenite—another parkinsonogenic toxin. Conversely, targeted deletion of Aqp9 in mice protects nigral dopaminergic neurons against MPP+ toxicity. A protective effect of Aqp9 deletion was demonstrated in organotypic slice cultures of mouse midbrain exposed to MPP+ in vitro and in mice subjected to intrastriatal injections of MPP+ in vivo. Seven days after intrastriatal MPP+ injections, the population of tyrosine hydroxylase-positive cells in substantia nigra is reduced by 48% in Aqp9 knockout mice compared with 67% in WT littermates. Our results show that AQP9 –selectively expressed in catecholaminergic neurons—is permeable to MPP+ and suggest that this aquaglyceroporin contributes to the selective vulnerability of nigral dopaminergic neurons by providing an entry route for parkinsonogenic toxins. To our knowledge this is the first evidence implicating a toxin permeable membrane channel in the pathophysiology of Parkinson’s disease.

• Moen, Ingrid; Ugland, Hege; Strömberg, Niklas; Sjöström, Eva; Karlsson, Anders & Ringstad, Lovisa [Show all 9 contributors for this article] (2018). Development of a novel in situ gelling skin dressing: Delivering high levels of dissolved oxygen at pH 5.5. Health Science Reports. 13(1), p. 101–113. doi: 10.1002/hsr2.57. Full text in Research Archive
• Prydz, Agnete; Stahl, Katja; Puchades, Maja Amedjkouh; Davarpaneh, Nina; Nadeem, Maria & Ottersen, Ole Petter [Show all 8 contributors for this article] (2017). Subcellular expression of aquaporin-4 in substantia nigra of normal and MPTP-treated mice. Neuroscience. ISSN 0306-4522. 359, p. 258–266. doi: 10.1016/j.neuroscience.2017.07.029. Full text in Research Archive Show summary

  Aquaporin-4 (AQP4) is the predominant water channel in mammalian CNS where it is localized at the perivascular astrocytic foot processes abutting brain microvessels. Several lines of evidence suggest that AQP4 is involved in important homeostatic functions and that mislocalization of the perivascular pool of AQP4 is implicated in several different brain disorders. A recent study suggests that the differential susceptibility of midbrain dopaminergic neurons to the parkinsonogenic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) depends on the expression of AQP4. Further, MRI studies of patients with Parkinson’s disease (PD) point to an excessive water accumulation in the substantia nigra (SN). This prompted us to investigate the cellular and subcellular distribution of AQP4 in mouse SN using immunofluorescence and quantitative immunogold cytochemistry. Compared with neocortex, SN exhibits a higher concentration of AQP4. Specifically, judged by electron microscopic immunogold analysis, the perivascular density of AQP4 in SN exceeds by 70% the perivascular density of AQP4 in the neocortex. An even larger difference in AQP4 labeling was found for astrocytic processes in the neuropil. Treatment with MPTP further increased (by >30%) the perivascular AQP4 density in SN, but also increased AQP4 labeling in the neocortex. Our data indicate that the perivascular AQP4 pool in SN is high in normal animals and even higher after treatment with MPTP. This would leave the SN more prone to water accumulation and supports the idea that AQP4 could be involved in the pathogenesis of PD.

• Katoozi, Shirin; Skauli, Nadia; Rahmani, Soulmaz; Camassa, Laura Maria Azzurra; Boldt, Henning Bunsow & Ottersen, Ole Petter [Show all 7 contributors for this article] (2017). Targeted deletion of Aqp4 promotes the formation of astrocytic gap junctions. Brain Structure and Function. ISSN 1863-2653. p. 1–14. doi: 10.1007/s00429-017-1448-5. Full text in Research Archive
• Nakayama, Shin; Amiry-Moghaddam, Mahmood; Ottersen, Ole Petter & Bhardwaj, Anish (2016). Conivaptan, a Selective Arginine Vasopressin V&lt;sub&gt;1a&lt;/sub&gt; and V&lt;sub&gt;2&lt;/sub&gt; Receptor Antagonist Attenuates Global Cerebral Edema Following Experimental Cardiac Arrest via Perivascular Pool of Aquaporin-4. Neurocritical Care. ISSN 1541-6933. 24(2), p. 273–282. doi: 10.1007/s12028-015-0236-4. Full text in Research Archive
• Huang, Wei; Li, Qing; Amiry-Moghaddam, Mahmood; Hokama, Madoka; Sardi, Sylvia H. & Nagao, Masashi [Show all 8 contributors for this article] (2016). Critical endothelial regulation by LRP5 during retinal vascular development. PLOS ONE. 11:e0152833(3). doi: 10.1371/journal.pone.0152833. Full text in Research Archive
• Nakayama, Shin; Migliati, Elton; Amiry-Moghaddam, Mahmood; Ottersen, Ole Petter & Bhardwaj, Anish (2016). Osmotherapy with hypertonic saline attenuates global cerebral edema following experimental cardiac arrest via perivascular pool of aquaporin-4. Critical Care Medicine. ISSN 0090-3493. 44(8), p. e702–e710. doi: 10.1097/CCM.0000000000001671. Full text in Research Archive
• Hoddevik, Eystein Hellstrøm; Khan, Faraz Hameed; Rahmani, Soulmaz; Ottersen, Ole Petter; Boldt, Henning Bunsow & Amiry-Moghaddam, Mahmood (2016). Factors determining the density of AQP4 water channel molecules at the brain-blood interface. Brain Structure and Function. ISSN 1863-2653. 222(4), p. 1753–1766. doi: 10.1007/s00429-016-1305-y. Full text in Research Archive Show summary

  Perivascular endfeet of astrocytes are enriched with aquaporin-4 (AQP4)—a water channel that is critically involved in water transport at the brain–blood interface and that recently was identified as a key molecule in a system for waste clearance. The factors that determine the size of the perivascular AQP4 pool remain to be identified. Here we show that the size of this pool differs considerably between brain regions, roughly mirroring regional differences in Aqp4 mRNA copy numbers. We demonstrate that a targeted deletion of α-syntrophin—a member of the dystrophin complex responsible for AQP4 anchoring—removes a substantial and fairly constant proportion (79–94 %) of the perivascular AQP4 pool across the central nervous system (CNS). Quantitative immunogold analyses of AQP4 and α-syntrophin in perivascular membranes indicate that there is a fixed stoichiometry between these two molecules. Both molecules occur at higher densities in endfoot membrane domains facing pericytes than in endfoot membrane domains facing endothelial cells. Our data suggest that irrespective of region, endfoot targeting of α-syntrophin is the single most important factor determining the size of the perivascular AQP4 pool and hence the capacity for water transport at the brain–blood interface.

• Ricanek, Petr; Lunde, Lisa Kristina; Frye, Stephan Alfons; Støen, Mari; Nygård, Ståle & Morth, Jens Preben [Show all 10 contributors for this article] (2015). Reduced expression of aquaporins in human intestinal mucosa in early stage inflammatory bowel disease. Clinical and Experimental Gastroenterology. 8, p. 49–67. doi: 10.2147/CEG.S70119. Full text in Research Archive
• Camassa, Laura Maria Azzurra; Lunde, Lisa Kristina; Hoddevik, Eystein Hellstrøm; Stensland, Maria; Boldt, Henning Bunsow & Souza, Gustavo Antonio De [Show all 8 contributors for this article] (2015). Mechanisms underlying AQP4 accumulation in astrocyte endfeet. Glia. ISSN 0894-1491. 63(11), p. 2073–2091. doi: 10.1002/glia.22878. Full text in Research Archive
• Lunde, Lisa Kristina; Camassa, Laura Maria Azzurra; Hoddevik, Eystein Hellstrøm; Khan, Faraz Hameed; Ottersen, Ole Petter & Boldt, Henning Bunsow [Show all 7 contributors for this article] (2014). Postnatal development of the molecular complex underlying astrocyte polarization. Brain Structure and Function. ISSN 1863-2653. 220(4), p. 2087–2101. doi: 10.1007/s00429-014-0775-z. Full text in Research Archive
• Rutkovskiy, Arkady; Bliksøen, Marte; Hillestad, Vigdis; Amin, Mubashar Mohammad; Czibik, Gabor Tamas & Valen, Guro [Show all 9 contributors for this article] (2013). Aquaporin-1 in cardiac endothelial cells is downregulated in ischemia, hypoxia, and cardioplegia. Journal of Molecular and Cellular Cardiology. ISSN 0022-2828. 56, p. 22–33. doi: 10.1016/j.yjmcc.2012.12.002. Full text in Research Archive
• Amiry-Moghaddam, Mahmood & Ottersen, Ole Petter (2013). Immunogold cytochemistry in neuroscience. Nature Neuroscience. ISSN 1097-6256. 16(7), p. 798–804. doi: 10.1038/nn.3418. Full text in Research Archive
• Nagelhus, Erlend Arnulf; Amiry-Moghaddam, Mahmood; Bergersen, Linda Hildegard; Bjaalie, Jan G.; Eriksson, Jens & Gundersen, Vidar [Show all 12 contributors for this article] (2013). The glia doctrine: Addressing the role of glial cells in healthy brain ageing. Mechanisms of Ageing and Development. ISSN 0047-6374. 134(10), p. 449–459. doi: 10.1016/j.mad.2013.10.001. Full text in Research Archive
• Magdolenova, Zuzana; Drlickova, Martina; Henjum, Kristi; Pran, Elise Rundén; Tulinska, Jana & Bilanicova, Dagmar [Show all 22 contributors for this article] (2013). Coating-dependent induction of cytotoxicity and genotoxicity of iron oxide nanoparticles. Nanotoxicology. ISSN 1743-5390. 9(1), p. 44–56. doi: 10.3109/17435390.2013.847505. Full text in Research Archive
• Promeneur, Dominique; Lunde, Lisa Kristina; Amiry-Moghaddam, Mahmood & Agre, Peter (2013). Protective role of brain water channel AQP4 in murine cerebral malaria. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 110(3), p. 1035–1040. doi: 10.1073/pnas.1220566110. Full text in Research Archive
• Nuruddin, Syed; Wojniusz, Slawomir; Ropstad, Erik; Krogenæs, Anette; Evans, Neil P. & Robinson, Jane E. [Show all 9 contributors for this article] (2013). Peri-pubertal gonadotropin-releasing hormone analog treatment affects hippocampus gene expression without changing spatial orientation in young sheep. Behavioural Brain Research. ISSN 0166-4328. 242, p. 9–16. doi: 10.1016/j.bbr.2012.12.027. Full text in Research Archive
• Alvestad, Silje; Hammer, Janniche; Hoddevik, Eystein Hellstrøm; Skare, Øivind; Sonnewald, Ursula & Amiry-Moghaddam, Mahmood [Show all 7 contributors for this article] (2013). Mislocalization of AQP4 precedes chronic seizures in the kainate model of temporal lobe epilepsy. Epilepsy Research. ISSN 0920-1211. 105(1-2), p. 30–41. doi: 10.1016/j.eplepsyres.2013.01.006. Full text in Research Archive
• Rutkovskiy, Arkady; Stensløkken, Kåre-Olav; Mariero, Lars Henrik; Skrbic, Biljana; Amiry-Moghaddam, Mahmood & Hillestad, Vigdis [Show all 12 contributors for this article] (2012). Aquaporin-4 in the heart: expression, regulation and functional role in ischemia. Basic Research in Cardiology. ISSN 0300-8428. 107, p. 280–280. doi: 10.1007/s00395-012-0280-6. Full text in Research Archive
• Kielland, Anders; Camassa, Laura Maria Azzurra; Døhlen, Gaute; Munthe, Ludvig Andre; Blomhoff, Rune & Amiry-Moghaddam, Mahmood [Show all 7 contributors for this article] (2012). Activity in Perinatal Brain During Infectious and Hypoxic-Ischemic Insults revealed by a Reporter Mouse. Brain Pathology. ISSN 1015-6305. 22(4), p. 499–510. doi: 10.1111/j.1750-3639.2011.00548.x. Full text in Research Archive
• Kielland, Anders; Camassa, Laura Maria Azzurra; Døhlen, Gaute; Munthe, Ludvig Andre; Blomhoff, Rune & Amiry-Moghaddam, Mahmood [Show all 7 contributors for this article] (2012). NF-kappa B Activity in Perinatal Brain During Infectious and Hypoxic-Ischemic Insults Revealed by a Reporter Mouse. Brain Pathology. ISSN 1015-6305. 22(4), p. 499–510. doi: 10.1111/j.1750-3639.2011.00548.x. Full text in Research Archive
• Jacobsen, Øyvind; Maekawa, Hiroaki; Ge, Nien-Hui; Gorbitz, Carl Henrik; Rongved, Pål & Ottersen, Ole Petter [Show all 8 contributors for this article] (2011). Stapling of a 3(10)-Helix with Click Chemistry. Journal of Organic Chemistry. ISSN 0022-3263. 76(5), p. 1228–1238. doi: 10.1021/jo101670a. Full text in Research Archive
• Stahl, Katja; Mylonakou, Maria-Niki; Skare, Øivind; Amiry-Moghaddam, Mahmood & Torp, Reidun (2011). Cytoprotective effects of growth factors: BDNF more potent than GDNF in an organotypic culture model of Parkinson's disease. Brain Research. ISSN 0006-8993. 1378, p. 105–118. doi: 10.1016/j.brainres.2010.12.090. Full text in Research Archive
• Benfenati, Valentina; Caprini, Marco; Dovizio, Melania; Mylonakou, Maria-Niki; Ferroni, Stefano & Ottersen, Ole Petter [Show all 7 contributors for this article] (2011). An aquaporin-4/transient receptor potential vanilloid 4 (AQP4/TRPV4) complex is essential for cell-volume control in astrocytes. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 108(6), p. 2563–2568. doi: 10.1073/pnas.1012867108. Full text in Research Archive
• Yang, Jing; Lunde, Lisa Kristina; Nuntagij, Paworn; Oguchi, Tomohiro; Camassa, Laura Maria Azzurra & Nilsson, Lars N. G. [Show all 11 contributors for this article] (2011). Loss of Astrocyte Polarization in the Tg-ArcSwe Mouse Model of Alzheimer's Disease. Journal of Alzheimer's Disease. ISSN 1387-2877. doi: 10.3233/JAD-2011-110725. Full text in Research Archive
• Liu, Xiaoqin; Nakayama, Shin; Amiry-Moghaddam, Mahmood Reza; Ottersen, Ole Petter & Bhardwaj, Anish (2010). Arginine-Vasopressin V-1 but not V-2 Receptor Antagonism Modulates Infarct Volume, Brain Water Content, and Aquaporin-4 Expression Following Experimental Stroke. Neurocritical Care. ISSN 1541-6933. 12(1), p. 124–131. doi: 10.1007/s12028-009-9277-x. Full text in Research Archive
• Berle, Magnus Foldal; Wester, Knut; Ulvik, Rune Johan; Haaland, Øystein Ariansen; Kroksveen, Ann Cathrine & Amiry-Moghaddam, Mahmood [Show all 8 contributors for this article] (2010). Arachnoid cysts do not contain cerebrospinal fluid: A comparative chemical analysis of arachnoid cyst fluid and cerebrospinal fluid in adults. Cerebrospinal Fluid Research. 7(1). doi: 10.1186/1743-8454-7-8. Full text in Research Archive Show summary

  Background Arachnoid cyst (AC) fluid has not previously been compared with cerebrospinal fluid (CSF) from the same patient. ACs are commonly referred to as containing "CSF-like fluid". The objective of this study was to characterize AC fluid by clinical chemistry and to compare AC fluid to CSF drawn from the same patient. Such comparative analysis can shed further light on the mechanisms for filling and sustaining of ACs. Methods Cyst fluid from 15 adult patients with unilateral temporal AC (9 female, 6 male, age 22-77y) was compared with CSF from the same patients by clinical chemical analysis. Results AC fluid and CSF had the same osmolarity. There were no significant differences in the concentrations of sodium, potassium, chloride, calcium, magnesium or glucose. We found significant elevated concentration of phosphate in AC fluid (0.39 versus 0.35 mmol/L in CSF; p = 0.02), and significantly reduced concentrations of total protein (0.30 versus 0.41 g/L; p = 0.004), of ferritin (7.8 versus 25.5 ug/L; p = 0.001) and of lactate dehydrogenase (17.9 versus 35.6 U/L; p = 0.002) in AC fluid relative to CSF. Conclusions AC fluid is not identical to CSF. The differential composition of AC fluid relative to CSF supports secretion or active transport as the mechanism underlying cyst filling. Oncotic pressure gradients or slit-valves as mechanisms for generating fluid in temporal ACs are not supported by these results.

• Migliati, Elton R.; Amiry-Moghaddam, Mahmood; Froehner, S.C.; Adams, Marvin E.; Ottersen, Ole Petter & Bhardwaj, Anish (2010). Na+-K+-2Cl(-) Cotransport Inhibitor Attenuates Cerebral Edema Following Experimental Stroke via the Perivascular Pool of Aquaporin-4. Neurocritical Care. ISSN 1541-6933. 13(1), p. 123–131. doi: 10.1007/s12028-010-9376-8. Full text in Research Archive
• Helland, Christian Andre; Aarhus, Mads; Knappskog, Per Morten; Olsson, Lisa K; Lund-Johansen, Morten & Amiry-Moghaddam, Mahmood Reza [Show all 7 contributors for this article] (2010). Increased NKCC1 expression in arachnoid cysts supports secretory basis for cyst formation. Experimental Neurology. ISSN 0014-4886. 224(2), p. 424–428. doi: 10.1016/j.expneurol.2010.05.002. Full text in Research Archive
• Jacobsen, Øyvind; Klaveness, Jo; Ottersen, Ole Petter; Amiry-Moghaddam, Mahmood Reza & Rongved, Pål (2009). Synthesis of cyclic peptide analogues of the 3(10) helical Pro138-Gly144 segment of human aquaporin-4 by olefin metathesis. Organic and biomolecular chemistry. ISSN 1477-0520. 7(8), p. 1599–1611. doi: 10.1039/b823559g. Full text in Research Archive
• Mylonakou, Maria-Niki; Petersen, Petur Henry; Rinvik, Eric; Rojek, Aleksandra; Valdimarsdottir, Erla & Zelenin, S [Show all 10 contributors for this article] (2009). Analysis of mice with targeted deletion of AQP9 gene provides conclusive evidence for expression of AQP9 in neurons. Journal of Neuroscience Research. ISSN 0360-4012. 87(6), p. 1310–1322. doi: 10.1002/jnr.21952. Full text in Research Archive
• Liu, Xiaoqin; Nakayama, Shin; Amiry-Moghaddam, Mahmood Reza; Ottersen, Ole Petter & Bhardwaj, A (2009). Arginine-Vasopressin V(1) but not V (2) Receptor Antagonism Modulates Infarct Volume, Brain Water Content, and Aquaporin-4 Expression Following Experimental Stroke. Neurocritical Care. ISSN 1541-6933. doi: 10.1007/s12028-009-9277-x. Full text in Research Archive
• Zeynalov, E; Chen, CH; Froehner, SC; Adams, ME; Ottersen, Ole Petter & Amiry-Moghaddam, Mahmood Reza [Show all 7 contributors for this article] (2008). The perivascular pool of aquaporin-4 mediates the effect of osmotherapy in postischemic cerebral edema. Critical Care Medicine. ISSN 0090-3493. 36, p. 2634–2640. doi: 10.1097/CCM.0b013e3181847853. Full text in Research Archive
• Liu, Xiaoqin; Zhang, Wenri; Alkayed, Nabil; Froehner, Stanley C.; Adams, Marvin E. & Amiry-Moghaddam, Mahmood Reza [Show all 9 contributors for this article] (2008). Lack of sex-linked differences in cerebral edema and aquaporin-4 expression after experimental stroke. Journal of Cerebral Blood Flow and Metabolism. ISSN 0271-678X. 28(12), p. 1898–1906. doi: 10.1038/jcbfm.2008.83. Full text in Research Archive
• Benfenati, Valentina; Amiry-Moghaddam, Mahmood Reza; Caprini, Melania; Mylonakou, Maria-Niki; Rapisarda, C & Ottersen, Ole Petter [Show all 7 contributors for this article] (2007). Expression and functional characterization of transient receptor potential vanilloid-related channel 4 (TRPV4) in rat cortical astrocytes. Neuroscience. ISSN 0306-4522. 148(4), p. 876–892. Full text in Research Archive
• Frydenlund, Didrik Søli; Bhardwaj, A; Otsuka, T; Mylonakou, Maria-Niki; Yasumura, T & Davidson, KGV [Show all 14 contributors for this article] (2006). Temporary loss of perivascular aquaporin-4 in neocortex after transient middle cerebral artery occlusion in mice. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 103, p. 13532–13536. Full text in Research Archive
• Warskulat, U; Borsch, E; Reinehr, R; Heller-Stilb, B; Monnighoff, I & Buchczyk, D [Show all 18 contributors for this article] (2006). Chronic liver disease is triggered by taurine transporter knockout in the mouse. The FASEB Journal. ISSN 0892-6638. 20. Full text in Research Archive
• Puwarawuttipanit, W; Bragg, AD; Frydenlund, Didrik Søli; Mylonakou, Maria-Niki; Nagelhus, Erlend Arnulf & Peters, MF [Show all 12 contributors for this article] (2006). Differential effect of alpha-syntrophin knockout on aquaporin-4 and Kir4.1 expression in retinal macroglial cells in mice. Neuroscience. ISSN 0306-4522. 137, p. 165–175. Full text in Research Archive
• Mathisen, Thomas Misje; Nagelhus, Erlend Arnulf; Juoleh, Bahareh; Torp, Reidun; Frydenlund, Didrik Søli & Mylonakou, Maria-Niki [Show all 18 contributors for this article] (2006). Postembedding Immunogold Cytochemistry of Membrane Molecules and Amino Acid Transmitters in the Central Nervous System. In Záborszky, L.; Wouterlood, F. & Lanciego, J.L. (Ed.), Neuroanatomical Tract Tracing: Molecules, Neurons, & Systems. Springer Science+Business Media B.V.. ISSN 9780387289410. p. 72–108. Full text in Research Archive
• Bragg, AD; Amiry-Moghaddam, Mahmood Reza; Ottersen, Ole Petter; Adams, ME & Froehner, SC (2006). Assembly of a perivascular astrocyte protein scaffold at the mammalian blood-brain barrier is dependent on alpha-syntrophin. Glia. ISSN 0894-1491. 53. Full text in Research Archive
• Bragg, AD; Amiry-Moghaddam, Mahmood; Ottersen, Ole Petter & Froehner, S.C. (2006). Assembly of a perivascular astrocyte protein scaffold at the mammalian blood-brain barrier is dependent on alpha-syntrophin. Glia. ISSN 0894-1491. Full text in Research Archive
• Eid, T; Lee, TSW; Thomas, Marion J.; Amiry-Moghaddam, Mahmood Reza; Bjørnsen, Lars Petter B. W. & Spencer, DD [Show all 9 contributors for this article] (2005). Loss of perivascular aquaporin 4 may underlie deficient water and K+ homeostasis in the human epileptogenic hippocampus. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 102, p. 1193–1198. Full text in Research Archive
• Solbu, Tom Tallak; Boulland, Jean-Luc; Zahid, W; Bredahl, May Kristin Lyamouri; Amiry-Moghaddam, Mahmood Reza & Storm-Mathisen, Jon [Show all 8 contributors for this article] (2005). Induction and targeting of the glutamine transporter SN1 to the basolateral membranes of cortical kidney tubule cells during chronic metabolic acidosis suggest a role in pH regulation. Journal of the American Society of Nephrology. ISSN 1046-6673. 16. Full text in Research Archive
• Amiry-Moghaddam, Mahmood Reza; Lindland, Heidi; Zelenin, S; Roberg, Bjørg Åse; Gundersen, BB & Petersen, Petur Henry [Show all 9 contributors for this article] (2005). Brain mitochondria contain aquaporin water channels: evidence for the expression of a short AQP9 isoform in the inner mitochondrial membrane. The FASEB Journal. ISSN 0892-6638. 19, p. 1459–1467. Full text in Research Archive
• Amiry-Moghadam, Mahmood Reza; Xue, R; Haug, Finn-Mogens Smejda; Neely, J.D.; Bhardwaj, A & Agre, P [Show all 10 contributors for this article] (2004). Alpha syntrophin deletion removes the perivascular but not the endothelial pool of aquaporin-4 at the blood-brain barrier and delays the development of brain edema in an experimental model of acute hyponatremia. The FASEB Journal. ISSN 0892-6638. 18(3), p. 542–544. Full text in Research Archive
• Amiry-Moghadam, Mahmood Reza; Frydenlund, Didrik Søli & Ottersen, Ole Petter (2004). Anchoring of aquaporin-4 in brain: Molecular mechanisms and implications forthe physiology and pathophysiology of water transport. Neuroscience. ISSN 0306-4522. 129(4), p. 997–1008. Full text in Research Archive
• Amiry-Moghadam, Mahmood Reza; Otsuka, T; Hurn, PD; Traystman, RJ; Haug, Finn-Mogens Smejda & Froehner, SC [Show all 11 contributors for this article] (2003). An alpha-syntrophin-dependent pool of AQP4 in astroglial end-feet confers bidirectional water flow between blood and brain. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 100(4), p. 2106–2111. Full text in Research Archive
• Amiry-Moghadam, Mahmood Reza; Williamson, A; Palomba, M; Eid, Tore; Lanerolle, NC de & Adams, ME [Show all 10 contributors for this article] (2003). Delayed K+ clearance and intensified seizures associated with Aquaporin-4 mislocalization: Phenotypic defects in brains of alpha-syntrophin-null mice. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 100(23), p. 13615–13620. Full text in Research Archive
• Amiry-Moghadam, Mahmood Reza & Ottersen, Ole Petter (2003). The molecular basis for water transport in brain. Nature Reviews Neuroscience. ISSN 1471-003X. 4(12), p. 991–1001. Full text in Research Archive
• Neely, J.D.; Amiry-Moghaddam, Mahmood; Ottersen, Ole Petter; Froehner, SC; Agre, P. & Adams, ME (2001). Syntrophin-dependent expression and localization of Aquaporin-4 water channel protein. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 98(24), p. 14108–14113. Full text in Research Archive
• Niermann, H.; Amiry-Moghaddam, Mahmood; Holthoff, K.; Witte, O.W. & Ottersen, Ole Petter (2001). A novel role of vasopressin in the brain: modulation of activity-dependent water flux in the neocortex. Journal of Neuroscience. ISSN 0270-6474. 21(9), p. 3045–3051. Full text in Research Archive
• Elkjaer, M; Vajda, Z.; Nejsum, L.N.; Kwon, T.; Jensen, U.B. & Amiry-Moghaddam, Mahmood Reza [Show all 7 contributors for this article] (2000). Immunolocalization of AQP9 in liver, epididymis, testis, spleen, and brain. Biochemical and Biophysical Research Communications - BBRC. ISSN 0006-291X. p. 1118–1128. Full text in Research Archive
• Wen, H. Z.; Nagelhus, Erlend Arnulf; Amiry-Moghaddam, Mahmood; Agre, P.; Ottersen, Ole Petter & Nielsen, S.P. (1999). Ontogeny of water transport in rat brain: postnatal expression of the aquaporin-4 water channel. European Journal of Neuroscience. ISSN 0953-816X. 11, p. 935–945. Full text in Research Archive
• Nielsen, S.P.; Nagelhus, Erlend Arnulf; Amiry-Moghaddam, Mahmood; Bourque, C.; Agre, P. & Ottersen, Ole Petter (1997). Specialized membrane domains for water transport in glial cells: High-resolution immunogold cytochemistry of Aquaporin-4 in rat brain. Journal of Neuroscience. ISSN 0270-6474. 17, p. 171–180. Full text in Research Archive
• Landsend, A. S.; Amiry-Moghaddam, Mahmood; Matsubara, Atsushi; Bergersen, Linda Hildegard; Usami, Shin-ichi & Wenthold, R.J. [Show all 7 contributors for this article] (1997). Differential localization of _d glutamate receptors in the rat cerebellum: coexpression with AMPA receptors in parallel fiber-spine synapses and absence from climbing fiber-spine synapses. Journal of Neuroscience. ISSN 0270-6474. 17, p. 834–842. Full text in Research Archive
• Nielsen, Søren; Nagelhus, Erlend Arnulf; Amiry-Moghaddam, Mahmood; Bourque, C.; Agre, P. & Ottersen, Ole Petter (1997). Specialized membrane domains for water transport in glial cells: high-resolution immunogold cytochemistry of aquaporin-4 in rat brain. Journal of Neuroscience. ISSN 0270-6474. Full text in Research Archive
• Landsend, Alf S.; Amiry-Moghaddam, Mahmood; Matsubara, Atsushi; Bergersen, Linda Hildegard; Usami, Shin-ichi & Wenthold, R.J. [Show all 7 contributors for this article] (1997). Differential localization of delta glutamate receptors in the rat cerebellum: coexpression with AMPA receptors in parallel fiber-spine synapses and absence from climbing fiber-spine synapses. Journal of Neuroscience. ISSN 0270-6474. Full text in Research Archive
• Amiry-Moghaddam, Mahmood Reza; Nagelhus, Erlend Arnulf; Agre, P.; Nielsen, S.P. & Ottersen, Ole Petter (1996). Taurine and water channels are colocalized in renal tubule cells and other tissues, Taurine 2. Plenum Press. p. 165–171. Full text in Research Archive
• Amiry-Moghaddam, Mahmood Reza; Nagelhus, Erlend Arnulf & Ottersen, Ole Petter (1994). Light- and electronmicroscopic distribution of taurine, an organic osmolyte, in rat renal tubule cells. Kidney International. ISSN 0085-2538. p. 10–22. Full text in Research Archive
• Nagelhus, Erlend Arnulf; Amiry-Moghaddam, Mahmood Reza; Lehmann, A. & Ottersen, Ole Petter (1994). Taurine as an organic osmolyte in the intact brain: immunocytochemical and biochemical studies. Advances in Experimental Medicine and Biology. ISSN 0065-2598. p. 325–334. Full text in Research Archive

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• Szu, Jenny; Parpura, Vladimir; Amiry-Moghaddam, Mahmood & Smith, Alex J. (2023). Editorial: Mechanisms and consequences of Aquaporin-4 redistribution in neurological disease. Frontiers in Cellular Neuroscience. 17. doi: 10.3389/fncel.2023.1143352. Full text in Research Archive
• Bjertness, Espen; Htay, Thein Thein; Maung, Nay Soe; Soe, Zaw Wai; Aye, Saw Sanda & Ottersen, Ole Petter [Show all 10 contributors for this article] (2016). E-learning resources in Myanmar. The Lancet. ISSN 0140-6736. 388(10063), p. 2990–2991. doi: 10.1016/S0140-6736(16)32520-X. Full text in Research Archive
• Olsen, Bjørn Reino; Amiry-Moghaddam, Mahmood & Ottersen, Ole Petter (2015). Translational Medical Research. In Laake, Petter; Benestad, Haakon Breien & Olsen, Bjørn Reino (Ed.), Research in Medical and Biological Sciences: From Planning and Preparation ot Grant Application and Publication.. Academic Press. ISSN 9780127999432. p. 213–235. Full text in Research Archive
• Witoszek, Nina & Amiry-Moghaddam, Mahmood (2014). "Hijab, galgen og revolusjon". Full text in Research Archive
• Amiry-Moghaddam, Mahmood (2010). Aquaporin water channels in health and disease. The FEBS Journal. ISSN 1742-464X. 277, p. 5–5. Full text in Research Archive
• Amiry-Moghaddam, Mahmood Reza; Hoddevik, Eystein Hellstrøm & Ottersen, Ole Petter (2010). AQUAPORINS: MULTIFARIOUS ROLES IN BRAIN. Neuroscience. ISSN 0306-4522. 168(4), p. 859–861. doi: 10.1016/j.neuroscience.2010.04.071. Full text in Research Archive
• Amiry-Moghaddam, Mahmood (2009). Aquaporin-4 water channels as new molecular targets in treatment of brain edema and stroke. Journal of the Neurological Sciences. ISSN 0022-510X. 285, p. S27–S27. Full text in Research Archive
• Amiry-Moghaddam, Mahmood Reza (2009). PHYSIOLOGICAL AND PATHOLOGICAL ROLES OF AQUAPORIN-4 IN THE BRAIN. Journal of Neurochemistry. ISSN 0022-3042. 110, p. 13–13. Full text in Research Archive
• Liu, X; Zhang, WR; Alkayed, NJ; Hurn, PD; Froehner, SC & Marvin, AE [Show all 9 contributors for this article] (2008). Lack of gender-linked differences in cerebral edema and aquaporin-4 expression after experimental stroke. Stroke. ISSN 0039-2499. 39, p. 672–673. Full text in Research Archive

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