Yun Zhou

• Verbruggen, Lise; Ates, Gamze; Lara, Olaya; Munck, Jolien De; Villers, Agnès & Pauw, Laura De [Vis alle 23 forfattere av denne artikkelen] (2022). Lifespan extension with preservation of hippocampal function in aged system x<inf>c</inf>⁻-deficient male mice. Molecular Psychiatry. ISSN 1359-4184. 27, s. 2355–2368. doi: 10.1038/s41380-022-01470-5. Fulltekst i vitenarkiv Vis sammendrag

  Abstract The cystine/glutamate antiporter system x c − has been identified as the major source of extracellular glutamate in several brain regions as well as a modulator of neuroinflammation, and genetic deletion of its specific subunit xCT (xCT −/− ) is protective in mouse models for age-related neurological disorders. However, the previously observed oxidative shift in the plasma cystine/cysteine ratio of adult xCT −/− mice led to the hypothesis that system x c − deletion would negatively affect life- and healthspan. Still, till now the role of system x c − in physiological aging remains unexplored. We therefore studied the effect of xCT deletion on the aging process of mice, with a particular focus on the immune system, hippocampal function, and cognitive aging. We observed that male xCT −/− mice have an extended lifespan, despite an even more increased plasma cystine/cysteine ratio in aged compared to adult mice. This oxidative shift does not negatively impact the general health status of the mice. On the contrary, the age-related priming of the innate immune system, that manifested as increased LPS-induced cytokine levels and hypothermia in xCT +/+ mice, was attenuated in xCT −/− mice. While this was associated with only a very moderate shift towards a more anti-inflammatory state of the aged hippocampus, we observed changes in the hippocampal metabolome that were associated with a preserved hippocampal function and the retention of hippocampus-dependent memory in male aged xCT −/− mice. Targeting system x c − is thus not only a promising strategy to prevent cognitive decline, but also to promote healthy aging.

• Farina, Maxwell G; Sandhu, Mani Ratnesh S; Parent, Maxime; Sanganahalli, Basavaraju G; Derbin, Matthew & Dhaher, Roni [Vis alle 12 forfattere av denne artikkelen] (2021). Small loci of astroglial glutamine synthetase deficiency in the postnatal brain cause epileptic seizures and impaired functional connectivity. Epilepsia. ISSN 0013-9580. 62, s. 2858–2870. doi: 10.1111/epi.17072. Fulltekst i vitenarkiv
• Danbolt, Niels Christian; López-Corcuera, Beatriz & Zhou, Yun (2021). Reconstitution of GABA, Glycine and Glutamate Transporters. Neurochemical Research. ISSN 0364-3190. 47, s. 85–110. doi: 10.1007/s11064-021-03331-z. Fulltekst i vitenarkiv Vis sammendrag

  Abstract In contrast to water soluble enzymes which can be purified and studied while in solution, studies of solute carrier (transporter) proteins require both that the protein of interest is situated in a phospholipid membrane and that this membrane forms a closed compartment. An additional challenge to the study of transporter proteins has been that the transport depends on the transmembrane electrochemical gradients. Baruch I. Kanner understood this early on and first developed techniques for studying plasma membrane vesicles. This advanced the field in that the experimenter could control the electrochemical gradients. Kanner, however, did not stop there, but started to solubilize the membranes so that the transporter proteins were taken out of their natural environment. In order to study them, Kanner then had to find a way to reconstitute them (reinsert them into phospholipid membranes). The scope of the present review is both to describe the reconstitution method in full detail as that has never been done, and also to reveal the scientific impact that this method has had. Kanner’s later work is not reviewed here although that also deserves a review because it too has had a huge impact.

• Zhou, Yun; Eid, Tore; Hassel, Bjørnar & Danbolt, Niels Christian (2020). Novel aspects of glutamine synthetase in ammonia homeostasis: Glutamine synthetase and ammonia. Neurochemistry International. ISSN 0197-0186. 140, s. 1–18. doi: 10.1016/j.neuint.2020.104809. Fulltekst i vitenarkiv
• Hu, Qiu Xiang; Klatt, Gesa; Gudmundsrud, Ruben; Ottestad-Hansen, Sigrid; Verbruggen, Lisa & Massie, Ann [Vis alle 8 forfattere av denne artikkelen] (2020). Semi-quantitative distribution of excitatory amino acid (glutamate) transporters 1-3 (EAAT1-3) and the cystine-glutamate exchanger (xCT) in the adult murine spinal cord. Neurochemistry International. ISSN 0197-0186. 140, s. 104811–104811. doi: 10.1016/j.neuint.2020.104811. Fulltekst i vitenarkiv Vis sammendrag

  Proper glutamatergic neurotransmission requires a balance between glutamate release and removal. The removal is mainly catalyzed by the glutamate transporters EAAT1-3, while the glutamate-cystine exchanger (system xc− with specific subunit xCT) represents one of the release mechanisms. Previous studies of the spinal cord have focused on the cellular distribution of EAAT1-3 with special reference to the dorsal horn, but have not provided quantitative data and have not systematically compared multiple segments. Here we have studied the distribution of EAAT1-3 and xCT in sections of multiple spinal cord segments using knockout tissue as negative controls. EAAT2 and EAAT3 were evenly expressed in all gray matter areas at all segmental levels, albeit with slightly higher levels in laminae 1–4 (dorsal horn). Somewhat higher levels of EAAT2 were also seen in lamina 9 (ventral horn), while EAAT3 was also detected in the lateral spinal nucleus. EAAT1 was concentrated in laminae 1–3, lamina 10, the intermediolateral nucleus and the sacral parasympathetic nucleus, while xCT was concentrated in laminae 1–3, lamina 10 and the leptomeninges. The levels of these four transporters were low in white matter, which represents 42% of the spinal cord volume. Quantitative immunoblotting revealed that the average level of EAAT1 in the whole spinal cord was 0.6 ± 0.1% of that in the cerebellum, while the levels of EAAT2, EAAT3 and xCT were, respectively, 41.6 ± 12%, 39.8 ± 7.6%, and 30.8 ± 4.3% of the levels in the hippocampus (mean values ± SEM). Conclusions: Because the hippocampal tissue content of EAAT2 protein is two orders of magnitude higher than the content of the EAAT3, it follows that most of the gray matter in the spinal cord depends almost exclusively on EAAT2 for glutamate removal, while the lamina involved in the processing of autonomic and nociceptive information rely on a complex system of transporters.

• Zhou, Yun; Hassel, Bjørnar; Eid, Tore & Danbolt, Niels Christian (2018). Axon-terminals expressing EAAT2 (GLT-1; Slc1a2) are common in the forebrain and not limited to the hippocampus. Neurochemistry International. ISSN 0197-0186. 123, s. 101–113. doi: 10.1016/j.neuint.2018.03.006. Fulltekst i vitenarkiv Vis sammendrag

  The excitatory amino acid transporter type 2 (EAAT2) represents the major mechanism for removal of extracellular glutamate. In the hippocampus, there is some EAAT2 in axon-terminals, whereas most of the protein is found in astroglia. The functional importance of the neuronal EAAT2 is unknown, and it is debated whether EAAT2-expressing nerve terminals are present in other parts of the brain. Here we selectively deleted the EAAT2 gene in neurons (by crossing EAAT2-flox mice with synapsin 1-Cre mice in the C57B6 background). To reduce interference from astroglial EAAT2, we measured glutamate accumulation in crude tissue homogenates. EAAT2 proteins levels were measured by immunoblotting. Although synapsin 1-Cre mediated gene deletion only reduced the forebrain tissue content of EAAT2 protein to 95.5 ± 3.4% of wild-type (littermate) controls, the glutamate accumulation in homogenates of neocortex, hippocampus, striatum and thalamus were nevertheless diminished to, respectively, 54 ± 4, 46 ± 3, 46 ± 2 and 65 ± 7% of controls (average ± SEM, n = 3 pairs of littermates). GABA uptake was unaffected. After injection of U-13C-glucose, lack of neuronal EAAT2 resulted in higher 13C-labeling of glutamine and GABA in the hippocampus suggesting that neuronal EAAT2 is partly short-circuiting the glutamate-glutamine cycle in wild-type mice. Crossing synapsin 1-Cre mice with Ai9 reporter mice revealed that Cre-mediated excision occurred efficiently in hippocampus CA3, but less efficiently in other regions and hardly at all in the cerebellum. Conclusions: (1) EAAT2 is expressed in nerve terminals in multiple brain regions. (2) The uptake catalyzed by neuronal EAAT2 plays a role in glutamate metabolism, at least in the hippocampus. (3) Synapsin 1-Cre does not delete floxed genes in all neurons, and the contribution of neuronal EAAT2 is therefore likely to be larger than revealed in the present study.

• Albertini, Giulia; Deneyer, L.; Hansen, Sigrid Ottestad; Zhou, Yun; Ates, G & Walrave, L [Vis alle 13 forfattere av denne artikkelen] (2018). Genetic deletion of xCT attenuates peripheral and central inflammation and mitigates LPS-induced sickness and depressive-like behavior in mice. Glia. ISSN 0894-1491. 66(9), s. 1845–1861. doi: 10.1002/glia.23343. Fulltekst i vitenarkiv Vis sammendrag

  The communication between the immune and central nervous system (CNS) is affected in many neurological disorders. Peripheral injections of the endotoxin lipopolysaccharide (LPS) are widely used to study this communication: an LPS challenge leads to a biphasic syndrome that starts with acute sickness and is followed by persistent brain inflammation and chronic behavioral alterations such as depressive-like symptoms. In vitro, the response to LPS treatment has been shown to involve enhanced expression of system. This cystine-glutamate antiporter, with xCT as specific subunit, represents the main glial provider of extracellular glutamate in mouse hippocampus. Here we injected male xCT knockout and wildtype mice with a single intraperitoneal dose of 5 mg/kg LPS. LPS-injection increased hippocampal xCT expression but did not alter the mainly astroglial localization of the xCT protein. Peripheral and central inflammation (as defined by cytokine levels and morphological activation of microglia) as well as LPS-induced sickness and depressive-like behavior were significantly attenuated in xCT-deficient mice compared with wildtype mice. Our study is the first to demonstrate the involvement of system in peripheral and central inflammation in vivo and the potential therapeutic relevance of its inhibition in brain disorders characterized by peripheral and central inflammation, such as depression.

• Hansen, Sigrid Ottestad; Hu, Qiu Xiang; Follin-Arbelet, Virginie; Bentea, Eduard; Sato, Hideyo & Massie, Ann [Vis alle 8 forfattere av denne artikkelen] (2018). The cystine-glutamate exchanger (xCT, Slc7a11) is expressed in significant concentrations in a subpopulation of astrocytes in the mouse brain. Glia. ISSN 0894-1491. 66(5), s. 951–970. doi: 10.1002/glia.23294. Fulltekst i vitenarkiv Vis sammendrag

  The cystine-glutamate exchanger (xCT) promotes glutathione synthesis by catalyzing cystine uptake and glutamate release. The released glutamate may modulate normal neural signaling and contribute to excitotoxicity in pathological situations. Uncertainty, however, remains as neither the expression levels nor the distribution of xCT have been unambiguously determined. In fact, xCT has been reported in astrocytes, neurons, oligodendrocytes and microglia, but most of the information derives from cell cultures. Here, we show by immunohistochemistry and by Western blotting that xCT is widely expressed in the central nervous system of both sexes. The labeling specificity was validated using tissue from xCT knockout mice as controls. Astrocytes were selectively labeled, but showed greatly varying labeling intensities. This astroglial heterogeneity resulted in an astrocyte domain-like labeling pattern. Strong xCT labeling was also found in the leptomeninges, along some blood vessels, in selected circumventricular organs and in a subpopulation of tanycytes residing the lateral walls of the ventral third ventricle. Neurons, oligodendrocytes and resting microglia, as well as reactive microglia induced by glutamine synthetase deficiency, were unlabeled. The concentration of xCT protein in hippocampus was compared with that of the EAAT3 glutamate transporter by immunoblotting using a chimeric xCT-EAAT3 protein to normalize xCT and EAAT3 labeling intensities. The immunoblots suggested an xCT/EAAT3 ratio close to one (0.75 ± 0.07; average ± SEM; n = 4) in adult C57BL6 mice. CONCLUSIONS: xCT is present in select blood/brain/CSF interface areas and in an astrocyte subpopulation, in sufficient quantities to support the notion that system xc- provides physiologically relevant transport activity.

• Zhou, Yun; Dhaher, Roni; Parent, Maxime; Hu, Qiu Xiang; Hassel, Bjørnar & Yee, Siu-Pok [Vis alle 10 forfattere av denne artikkelen] (2018). Selective deletion of glutamine synthetase in the mouse cerebral cortex induces glial dysfunction and vascular impairment that precede epilepsy and neurodegeneration. Neurochemistry International. ISSN 0197-0186. s. 1–12. doi: 10.1016/j.neuint.2018.07.009. Fulltekst i vitenarkiv Vis sammendrag

  Glutamate-ammonia ligase (glutamine synthetase; Glul) is enriched in astrocytes and serves as the primary enzyme for ammonia detoxification and glutamate inactivation in the brain. Loss of astroglial Glul is reported in hippocampi of epileptic patients, but the mechanism by which Glul deficiency might cause disease remains elusive. Here we created a novel mouse model by selectively deleting Glul in the hippocampus and neocortex. The Glul deficient mice were born without any apparent malformations and behaved unremarkably until postnatal week three. There were reductions in tissue levels of aspartate, glutamate, glutamine and GABA and in mRNA encoding glutamate receptor subunits GRIA1 and GRIN2A as well as in the glutamate transporter proteins EAAT1 and EAAT2. Adult Glul-deficient mice developed progressive neurodegeneration and spontaneous seizures which increased in frequency with age. Importantly, progressive astrogliosis occurred before neurodegeneration and was first noted in astrocytes along cerebral blood vessels. The responses to CO2-provocation were attenuated at four weeks of age and dilated microvessels were observed histologically in sclerotic areas of cKO. Thus, the abnormal glutamate metabolism observed in this model appeared to cause epilepsy by first inducing gliopathy and disrupting the neurovascular coupling.

• Hu, Qiu Xiang; Hansen, Sigrid Ottestad; Holmseth, Silvia; Hassel, Bjørnar; Danbolt, Niels Christian & Zhou, Yun (2018). Expression of glutamate transporters in mouse liver, kidney, and intestine. Journal of Histochemistry and Cytochemistry. ISSN 0022-1554. 66(3), s. 189–202. doi: 10.1369/0022155417749828. Fulltekst i vitenarkiv Vis sammendrag

  Glutamate transport activities have been identified not only in the brain, but also in the liver, kidney, and intestine. Although glutamate transporter distributions in the central nervous system are fairly well known, there are still uncertainties with respect to the distribution of these transporters in peripheral organs. Quantitative information is mostly lacking, and few of the studies have included genetically modified animals as specificity controls. The present study provides validated qualitative and semi-quantitative data on the excitatory amino acid transporter (EAAT)1-3 subtypes in the mouse liver, kidney, and intestine. In agreement with the current view, we found high EAAT3 protein levels in the brush borders of both the distal small intestine and the renal proximal tubules. Neither EAAT1 nor EAAT2 was detected at significant levels in murine kidney or intestine. In contrast, the liver only expressed EAAT2 (but 2 C-terminal splice variants). EAAT2 was detected in the plasma membranes of perivenous hepatocytes. These cells also expressed glutamine synthetase. Conditional deletion of hepatic EAAT2 did neither lead to overt neurological disturbances nor development of fatty liver.

• Eid, Tore; Gruenbaum, SE; Dhaher, R; Lee, T W; Zhou, Yun & Danbolt, Niels Christian (2016). The Glutamate-Glutamine Cycle in Epilepsy. Advances in neurobiology. ISSN 2190-5215. 13, s. 351–400. doi: 10.1007/978-3-319-45096-4_14. Fulltekst i vitenarkiv
• Danbolt, Niels Christian; Furness, David N & Zhou, Yun (2016). Neuronal vs glial glutamate uptake: Resolving the conundrum. Neurochemistry International. ISSN 0197-0186. 98, s. 29–45. doi: 10.1016/j.neuint.2016.05.009. Fulltekst i vitenarkiv Vis sammendrag

  Neither normal brain function nor the pathological processes involved in neurological diseases can be adequately understood without knowledge of the release, uptake and metabolism of glutamate. The reason for this is that glutamate (a) is the most abundant amino acid in the brain, (b) is at the cross-roads between several metabolic pathways, and (c) serves as the major excitatory neurotransmitter. In fact most brain cells express glutamate receptors and are thereby influenced by extracellular glutamate. In agreement, brain cells have powerful uptake systems that constantly remove glutamate from the extracellular fluid and thereby limit receptor activation. It has been clear since the 1970s that both astrocytes and neurons express glutamate transporters. However the relative contribution of neuronal and glial transporters to the total glutamate uptake activity, however, as well as their functional importance, has been hotly debated ever since. The present short review provides (a) an overview of what we know about neuronal glutamate uptake as well as an historical description of how we got there, and (b) a hypothesis reconciling apparently contradicting observations thereby possibly resolving the paradox.

• Danbolt, Niels Christian; Zhou, Yun; Furness, David N & Holmseth, Silvia (2016). Strategies for immunohistochemical protein localization using antibodies: What did we learn from neurotransmitter transporters in glial cells and neurons. Glia. ISSN 0894-1491. 64(12), s. 2045–2064. doi: 10.1002/glia.23027. Fulltekst i vitenarkiv Vis sammendrag

  Immunocytochemistry and Western blotting are still major methods for protein localization, but they rely on the specificity of the antibodies. Validation of antibody specificity remains challenging mostly because ideal negative controls are often unavailable. Further, immunochemical labeling patterns are also influenced by a number of other factors such as postmortem changes, fixation procedures and blocking agents as well as the general assay conditions (e.g., buffers, temperature, etc.). Western blotting similarly depends on tissue collection and sample preparation as well as the electrophoretic separation, transfer to blotting membranes and the immunochemical probing of immobilized molecules. Publication of inaccurate information on protein distribution has downstream consequences for other researchers because the interpretation of physiological and pharmacological observations depends on information on where ion channels, receptors, enzymes or transporters are located. Despite numerous reports, some of which are strongly worded, erroneous localization data are being published. Here we describe the extent of the problem and illustrate the nature of the pitfalls with examples from studies of neurotransmitter transporters. We explain the importance of supplementing immunochemical observations with other measurements (e.g., mRNA levels and distribution, protein activity, mass spectrometry, electrophysiological recordings, etc.) and why quantitative considerations are integral parts of the quality control. Further, we propose a practical strategy for researchers who plan to embark on a localization study. We also share our thoughts about guidelines for quality control.

• Petr, Geraldine T; Sun, Yan; Frederick, Natalie M; Zhou, Yun; Dhamne, Sameer C & Hameed, Mustafa Q [Vis alle 15 forfattere av denne artikkelen] (2015). Conditional deletion of the glutamate transporter GLT-1 reveals that astrocytic GLT-1 protects against fatal epilepsy while neuronal GLT-1 contributes significantly to glutamate uptake into synaptosomes. Journal of Neuroscience. ISSN 0270-6474. 35(13), s. 5187–5201. doi: 10.1523/JNEUROSCI.4255-14.2015. Fulltekst i vitenarkiv
• Zhou, Yun; Kempson, S.A. & Danbolt, Niels Christian (2015). Betaine uptake with a focus on the betaine/GABA transporter. Food and Nutritional Components in Focus. ISSN 2045-1695. 2015-January(7), s. 76–89. doi: 10.1039/9781782628446-00076. Fulltekst i vitenarkiv
• Zhou, Yun & Danbolt, Niels Christian (2014). Glutamate as a neurotransmitter in the healthy brain. Journal of Neural Transmission. ISSN 0300-9564. 121(8), s. 799–817. doi: 10.1007/s00702-014-1180-8. Fulltekst i vitenarkiv Vis sammendrag

  Glutamate is the most abundant free amino acid in the brain and is at the crossroad between multiple metabolic pathways. Considering this, it was a surprise to discover that glutamate has excitatory effects on nerve cells, and that it can excite cells to their death in a process now referred to as “excitotoxicity”. This effect is due to glutamate receptors present on the surface of brain cells. Powerful uptake systems (glutamate transporters) prevent excessive activation of these receptors by continuously removing glutamate from the extracellular fluid in the brain. Further, the blood–brain barrier shields the brain from glutamate in the blood. The highest concentrations of glutamate are found in synaptic vesicles in nerve terminals from where it can be released by exocytosis. In fact, glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. It took, however, a long time to realize that. The present review provides a brief historical description, gives a short overview of glutamate as a transmitter in the healthy brain, and comments on the so-called glutamate–glutamine cycle. The glutamate transporters responsible for the glutamate removal are described in some detail. Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

• Zhou, Yun; Wang, Xiaoyu; Tzingounis, Anastasios V; Danbolt, Niels Christian & Larsson, H Peter (2014). EAAT2 (GLT-1; slc1a2) glutamate transporters reconstituted in liposomes argues against heteroexchange being substantially faster than net uptake. Journal of Neuroscience. ISSN 0270-6474. 34(40), s. 13472–13485. doi: 10.1523/JNEUROSCI.2282-14.2014. Fulltekst i vitenarkiv
• Zhou, Yun; Waanders, LF; Holmseth, Silvia; Guo, C; Berger, Urs V & Li, Yuchuan [Vis alle 9 forfattere av denne artikkelen] (2014). Proteome analysis and conditional deletion of the EAAT2 glutamate transporter provide evidence against a role of EAAT2 in pancreatic insulin secretion in mice. Journal of Biological Chemistry. ISSN 0021-9258. 289(3), s. 1329–1344. doi: 10.1074/jbc.M113.529065. Fulltekst i vitenarkiv
• Zhou, Yun & Danbolt, Niels Christian (2013). GABA and Glutamate Transporters in Brain. Frontiers in Endocrinology. 4. doi: 10.3389/fendo.2013.00165. Fulltekst i vitenarkiv
• Bjørnsen, Lars Petter; Hadera, Mussie Ghezu; Zhou, Yun; Danbolt, Niels Christian & Sonnewald, Ursula (2013). The GLT-1 (EAAT2; Slc1a2) glutamate transporter is essential for glutamate homeostasis in the neocortex of the mouse. Journal of Neurochemistry. ISSN 0022-3042. 128(5), s. 641–649. doi: 10.1111/jnc.12509. Fulltekst i vitenarkiv
• Zhou, Yun; Waanders, Leonie; Holmseth, Silvia; Guo, Caiying; Berger, Urs V & Li, Yuchuan [Vis alle 9 forfattere av denne artikkelen] (2013). Proteome analysis and conditional deletion of the EAAT2 glutamate transporter provide evidence against a role of EAAT2 in pancreatic insulin secretion in mice. Journal of Biological Chemistry. ISSN 0021-9258. doi: 10.1074/jbc.M113.529065. Fulltekst i vitenarkiv
• Zhou, Yun; Holmseth, Silvia; Hua, Rui; Lehre, Anne- Catherine W G; Olofsson, Anna Maria & Poblete-Naredo, Irais [Vis alle 8 forfattere av denne artikkelen] (2012). The betaine-GABA transporter (BGT1, slc6a12) is predominantly expressed in the liver and at lower levels in the kidneys and at the brain surface. American Journal of Physiology - Renal, fluid and electrolyte physiology. ISSN 0363-6127. 302(3), s. F316–F328. doi: 10.1152/ajprenal.00464.2011. Fulltekst i vitenarkiv
• Holmseth, Silvia; Zhou, Yun; Follin-Arbelet, Virginie; Lehre, Knut Petter Dæhlin; Bergles, Dwight E. & Danbolt, Niels Christian (2012). Specificity Controls for Immunocytochemistry: The Antigen Preadsorption Test Can Lead to Inaccurate Assessment of Antibody Specificity. Journal of Histochemistry and Cytochemistry. ISSN 0022-1554. 60(3), s. 174–187. doi: 10.1369/0022155411434828. Fulltekst i vitenarkiv
• Holmseth, Silvia; Dehnes, Yvette; Huang, YHH; Follin-Arbelet, Virginie; Verket, Nina Julie & Mylonakou, Maria-Niki [Vis alle 12 forfattere av denne artikkelen] (2012). The Density of EAAC1 (EAAT3) Glutamate Transporters Expressed by Neurons in the Mammalian CNS. Journal of Neuroscience. ISSN 0270-6474. 32(17), s. 6000–6013. doi: 10.1523/JNEUROSCI.5347-11.2012. Fulltekst i vitenarkiv
• Li, Yuchuan; Zhou, Yun & Danbolt, Niels Christian (2012). The Rates of Postmortem Proteolysis of Glutamate Transporters Differ Dramatically between Cells and between Transporter Subtypes. Journal of Histochemistry and Cytochemistry. ISSN 0022-1554. 60(11), s. 811–821. doi: 10.1369/0022155412458589. Fulltekst i vitenarkiv
• Zhou, Yun; Holmseth, Silvia; Guo, C; Hassel, Bjørnar; Höfner, G & Huitfeldt, Henrik [Vis alle 8 forfattere av denne artikkelen] (2012). Deletion of the γ-aminobutyric acid transporter 2 (GAT2 and SLC6A13) gene in mice leads to changes in liver and brain taurine contents. Journal of Biological Chemistry. ISSN 0021-9258. doi: 10.1074/jbc.M112.368175. Fulltekst i vitenarkiv Vis sammendrag

  The GABA transporters (GAT1, GAT2, GAT3, and BGT1) have mostly been discussed in relation to their potential roles in controlling the action of transmitter GABA in the nervous system. We have generated the first mice lacking the GAT2 (slc6a13) gene. Deletion of GAT2 (both mRNA and protein) neither affected growth, fertility, nor life span under nonchallenging rearing conditions. Immunocytochemistry showed that the GAT2 protein was predominantly expressed in the plasma membranes of periportal hepatocytes and in the basolateral membranes of proximal tubules in the renal cortex. This was validated by processing tissue from wild-type and knockout mice in parallel. Deletion of GAT2 reduced liver taurine levels by 50%, without affecting the expression of the taurine transporter TAUT. These results suggest an important role for GAT2 in taurine uptake from portal blood into liver. In support of this notion, GAT2-transfected HEK293 cells transported [3H]taurine. Furthermore, most of the uptake of [3H]GABA by cultured rat hepatocytes was due to GAT2, and this uptake was inhibited by taurine. GAT2 was not detected in brain parenchyma proper, excluding a role in GABA inactivation. It was, however, expressed in the leptomeninges and in a subpopulation of brain blood vessels. Deletion of GAT2 increased brain taurine levels by 20%, suggesting a taurine-exporting role for GAT2 in the brain.

• Lehre, Anne- Catherine W G; Rowley, Nicole; Zhou, Yun; Holmseth, Silvia; Guo, Chungang & Holen, Torgeir [Vis alle 16 forfattere av denne artikkelen] (2011). Deletion of the betaine-GABA transporter (BGT1; slc6a12) gene does not affect seizure thresholds of adult mice. Epilepsy Research. ISSN 0920-1211. 95(1-2), s. 70–81. doi: 10.1016/j.eplepsyres.2011.02.014. Fulltekst i vitenarkiv
• Furness, DN; Dehnes, Yvette; Akhtar, Aisha Qureshi; Rossi, DJ; Hamann, M & Grutle, Nina J. [Vis alle 14 forfattere av denne artikkelen] (2008). A QUANTITATIVE ASSESSMENT OF GLUTAMATE UPTAKE INTO HIPPOCAMPAL SYNAPTIC TERMINALS AND ASTROCYTES: NEW INSIGHTS INTO A NEURONAL ROLE FOR EXCITATORY AMINO ACID TRANSPORTER 2 (EAAT2). Neuroscience. ISSN 0306-4522. 157(1), s. 80–94. doi: 10.1016/j.neuroscience.2008.08.043. Fulltekst i vitenarkiv

Se alle arbeider i NVA

• Zhou, Yun & Danbolt, Niels Christian (2024). The brain in a glutamate storm. Fulltekst i vitenarkiv
• Zhou, Yun & Danbolt, Niels Christian (2024). Astroglial Glutamine Synthetase and the Pathogenesis of Epilepsy. Fulltekst i vitenarkiv
• Scott, Andrew J; O’Brien, Alexandra; Wilder-Romans, Kari; Elson, Brynn; Parsels, Joshua D. & Peterson, Erik R. [Vis alle 19 forfattere av denne artikkelen] (2024). Brain Tumors Hijack Glutamine From the Neurometabolic Microenvironment. Fulltekst i vitenarkiv
• Zhou, Yun & Danbolt, Niels Christian (2024). Glutamine Synthetase and the Pathogenesis of Epilepsy. Fulltekst i vitenarkiv
• Rise, Anne-Sofie; Klatt, Gesa Mirjam; Zhou, Yun & Danbolt, Niels Christian (2023). Determination of the Number of Astroglia In the Rodent Brain. Fulltekst i vitenarkiv
• Sem, Phillip; Zhou, Yun & Danbolt, Niels Christian (2023). A Whole-Brain Map of GABA Transporters in Rodent Brain. Fulltekst i vitenarkiv
• Zhou, Yun & Danbolt, Niels Christian (2022). Have you tasted some (betaine)? Fulltekst i vitenarkiv
• Zhou, Yun & Danbolt, Niels Christian (2022). Novel Aspects of Glutamine Synthetase in Ammonia homeostasis. Fulltekst i vitenarkiv
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• Zhou, Yun (2020). GABA uptake-functional roles of non-GAT1 transporters. Fulltekst i vitenarkiv
• Klatt, Gesa Mirjam; Hu, Qiu Xiang; Gudmundsrud, Ruben; Ottestad-Hansen, Sigrid; Verbruggen, Lisa & Massie, Ann [Vis alle 8 forfattere av denne artikkelen] (2020). Semi-quantitative distribution of excitatory amino acid (glutamate) transporters 1-3 (EAAT1-3) and the cystine-glutamate exchanger (xCT) in the adult murine spinal cord. Fulltekst i vitenarkiv
• Danbolt, Niels Christian & Zhou, Yun (2019). The Functional Importance of Neuronal vs Glial Glutamate Uptake. Fulltekst i vitenarkiv
• Zhou, Yun & Danbolt, Niels Christian (2019). Glutamate Transporters with Dual Personality. Fulltekst i vitenarkiv
• Hu, Qiu Xiang; Klatt, Gesa; Ottestad-Hansen, Sigrid; Gudmundsrud, Ruben; Massie, Ann & Danbolt, Niels Christian [Vis alle 7 forfattere av denne artikkelen] (2019). Differential Distribution of Glutamate Transporters EAAT1-3 and xCT in murine spinal cord: a semi-quantitative study. Fulltekst i vitenarkiv
• Hu, Qiu Xiang; Zhou, Yun & Danbolt, Niels Christian (2019). The concentration of GABA transporter proteins GAT1 and GAT3 in young adult mouse brain relative to those of glutamate transporter proteins. Fulltekst i vitenarkiv
• Zhou, Yun (2018). Glutamate uptake in nerve terminals. Fulltekst i vitenarkiv
• Zhou, Yun (2018). Neuronal vs glial glutamate uptake: Resolving the conundrum. Fulltekst i vitenarkiv
• Zhou, Yun; Hassel, Bjørnar; Eid, Tore & Danbolt, Niels Christian (2018). Axon-terminals expressing EAAT2 (GLT-1; slc1a2) are common in the forebrain and not limited to the hippocampus. Fulltekst i vitenarkiv
• Gudmundsrud, Ruben; Ottestad-Hansen, Sigrid; Hu, Qiu Xiang; Danbolt, Niels Christian & Zhou, Yun (2018). The role of glutamate/cystine exchanger (slc7a11) in amyotrophic lateral sclerosis. Fulltekst i vitenarkiv
• Danbolt, Niels Christian; Ottestad-Hansen, Sigrid; Hu, Qiu Xiang; Follin-Arbelet, Virginie; Bentea, Eduard & Sato, Hideyo [Vis alle 8 forfattere av denne artikkelen] (2018). The cysteine-glutamate exchanger (xCT, slc7a11) is expressed in significant concentrations in a subpopulation of astrocytes in the mouse brain. Fulltekst i vitenarkiv
• Ottestad-Hansen, Sigrid; Hu, Qiu Xiang; Follin-Arbelet, Virginie; Sato, Hideyo; Bentea, Eduard & Massie, Ann [Vis alle 8 forfattere av denne artikkelen] (2017). The cystine-glutamate exchanger (xCT, Slc7a11) is expressed in significant concentrations in a subpopulation of astrocytes in the mouse brain. Fulltekst i vitenarkiv
• Danbolt, Niels Christian; Zhou, Yun; Dhaher, Roni; Parent, Maxime; Yee, Siu-Pok & Hyder, Fahmeed [Vis alle 8 forfattere av denne artikkelen] (2017). Loss of glutamine synthetase initiates a sequence of neuropathological events that culminate in epilepsy and neurodegeneration. Fulltekst i vitenarkiv
• Hu, Qiu Xiang; Danbolt, Niels Christian; Eid, Tore & Zhou, Yun (2017). Phenotypic differences between brain- and liver-specific glutamine synthetase knockout mice. Fulltekst i vitenarkiv
• Ottestad-Hansen, Sigrid; Zhou, Yun; Follin-Arbelet, Virginie; Sato, Hideyo; Massie, Ann & Danbolt, Niels Christian (2016). The localization of glutamate-cystine exchanger xCT (slc7a11) in mouse brain. Fulltekst i vitenarkiv
• Hu, Qiu Xiang; Ottestad-Hansen, Sigrid; Kavanaugh, M.; Danbolt, Niels Christian & Zhou, Yun (2016). Vizualization of the EAAT3 glutamate transporter EAAC1 in mouse kidney and intestine. Fulltekst i vitenarkiv
• Danbolt, Niels Christian; Zhou, Yun; Xu, Ji & Khakh, Baljit (2015). Generation and characterization of BAC transgenic GABA transporter 2 (GAT2; slc6a13) tdTomato reporter mice. Fulltekst i vitenarkiv
• Zhou, Yun; Corbin, Karen; Xiang, Yi-Kong; Eskild, Winnie; Zeisel, Steven H. & Danbolt, Niels Christian (2015). The betaine-GABA transporter (BGT1; slc6a12) is not involved in the inactivation of transmitter GABA, but plays a role in preserving the choline levels in the liver. Fulltekst i vitenarkiv
• Danbolt, Niels Christian; Zhou, Yun; Xu, Ji & Khakh, Baljit (2015). Generation and characterization of BAC transgenic GABA transporter 2 (GAT2; slc6a13) tdTomato reporter mice. Fulltekst i vitenarkiv
• Wang, Helen; Dhaher, Roni; Farina, M.; Zhou, Yun; Yee, Siu-Pok & Danbolt, Niels Christian [Vis alle 7 forfattere av denne artikkelen] (2015). Brain site specific suppression of glutamine synthetase in mice using an adenoassociated virus knockout approach. Fulltekst i vitenarkiv
• Wang, Helen; Dhaher, Roni; Farina, M.; Zhou, Yun; Yee, Siu-Pok & Danbolt, Niels Christian [Vis alle 7 forfattere av denne artikkelen] (2015). Brain site specific suppression of glutamine synthetase in mice using an adenoassociated virus knockout approach. Fulltekst i vitenarkiv
• Zhou, Yun; Corbin, Karen; Xiang, Yi-Kong; Eskild, Winnie; Zeisel, Steven H. & Danbolt, Niels Christian (2015). The betaine-GABA transporter (BGT1; slc6a12) may play its main roles in the liver rather than in the brain. Fulltekst i vitenarkiv
• Zhou, Yun; Danbolt, Niels Christian & Kempson, S.A. (2014). The Betaine-GABA transporter. I Preedy, Victor R. (Red.), Betaine - Chemistry, Analysis, Function and Effects. Royal Society of Chemistry (RSC). ISSN 9781849738866. Fulltekst i vitenarkiv
• Kempson, SA; Zhou, Yun & Danbolt, Niels Christian (2014). The betaine/GABA transporter and betaine: Roles in brain, kidney, and liver. Frontiers in Physiology. 5 APR. doi: 10.3389/fphys.2014.00159. Fulltekst i vitenarkiv
• Hadera, Mussie Ghezu; Bjørnsen, Lars Petter; Zhou, Yun; Sonnewald, Ursula & Danbolt, Niels Christian (2013). Impairment of glial-neuronal interaction in GLT-1 knockout mice: an NMR spectroscopy study. Journal of Neurochemistry. ISSN 0022-3042. 125, s. 109–109. Fulltekst i vitenarkiv
• Hadera, Mussie Ghezu; Bjørnsen, Lars Petter; Zhou, Yun; Sonnewald, Ursula & Danbolt, Niels Christian (2013). Impairment of glial-neuronal interaction in GLT-1 knockout mice: an NMR spectroscopy study. Fulltekst i vitenarkiv
• Danbolt, Niels Christian; Holmseth, Silvia; Dehnes, Yvette; Huang, Y.; Follin-Arbelet, Virginie & Grutle, N [Vis alle 11 forfattere av denne artikkelen] (2011). QUANTIFICATION AND LOCALIZATION OF THE EAAC1 GLUTAMATE TRANSPORTER IN BRAIN. Glia. ISSN 0894-1491. 59, s. S66–S66. Fulltekst i vitenarkiv
• Zhou, Yun; Holmseth, Silvia; Holen, Torgeir & Danbolt, Niels Christian (2011). EVIDENCE AGAINST A ROLE OF THE BETAINE-GABA TRANSPORTER (BGT1, SLC6A12) IN THE CONTROL OF GABA RECEPTOR ACTIVATION. Glia. ISSN 0894-1491. 59, s. S69–S70. Fulltekst i vitenarkiv

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