Sigrid Ottestad-Hansen

• Verbruggen, Lise; Ates, Gamze; Lara, Olaya; De Munck, Jolien; Villers, Agnès & De Pauw, Laura [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
• Dhaher, Roni; Gruenbaum, Shaun E.; Sandhu, Mani Ratnesh; Ottestad-Hansen, Sigrid; Tu, Nathan & Wang, Yue [Vis alle 12 forfattere av denne artikkelen] (2021). Network-Related Changes in Neurotransmitters and Seizure Propagation During Rodent Epileptogenesis. Neurology. ISSN 0028-3878. 96(18), s. e2261–e2271. doi: 10.1212/WNL.0000000000011846.
• 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. doi: 10.1016/j.neuint.2020.104811. Fulltekst i vitenarkiv
• 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. 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.

• 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.

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• 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.
• 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.

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