@article{a4ec00603a8c42c5977e65819d7108be,
title = "Evidence for glutamine synthetase function in mouse spinal cord oligodendrocytes",
abstract = "Glutamine synthetase (GS) is a key enzyme that metabolizes glutamate into glutamine. While GS is highly enriched in astrocytes, expression in other glial lineages has been noted. Using a combination of reporter mice and cell type-specific markers, we show that GS is expressed in myelinating oligodendrocytes (OL) but not oligodendrocyte progenitor cells of the mouse and human ventral spinal cord. To investigate the role of GS in mature OL, we used a conditional knockout (cKO) approach to selectively delete GS-encoding gene (Glul) in OL, which caused a significant decrease in glutamine levels on mouse spinal cord extracts. GS cKO mice (CNP-cre+:Glulfl/fl) showed no differences in motor neuron numbers, size or axon density; OL differentiation and myelination in the ventral spinal cord was normal up to 6 months of age. Interestingly, GS cKO mice showed a transient and specific decrease in peak force while locomotion and motor coordination remained unaffected. Last, GS expression in OL was increased in chronic pathological conditions in both mouse and humans. We found a disease-stage dependent increase of OL expressing GS in the ventral spinal cord of SOD1(G93A) mouse model of amyotrophic lateral sclerosis. Moreover, we showed that GLUL transcripts levels were increased in OL in leukocortical tissue from multiple sclerosis but not control patients. These findings provide evidence towards OL-encoded GS function in spinal cord sensorimotor axis, which is dysregulated in chronic neurological diseases.",
keywords = "amyotrophic lateral sclerosis, glutamine synthetase, motor neurons, oligodendrocytes, peak strength, spinal cord",
author = "\{Ben Haim\}, Lucile and Lucas Schirmer and Amel Zulji and Khalida Sabeur and Brice Tiret and Matthieu Ribon and Sandra Chang and Lamers, \{Wouter H.\} and Boill{\'e}e, \{S. verine\} and Chaumeil, \{Myriam M.\} and Rowitch, \{David H.\}",
note = "Funding Information: We thank Dr. S. Fancy for providing mice (originally developed by Dr. A. Nishiyama) and Dr. M. Chavali for technical help. We thank Drs. C. Escartin and C. Lobsiger for inputs on the project, critical reading of the manuscript and feedback on figures. This work was supported by: the Wellcome Trust, NIH NINDS (P01NS083513) and ERC Advanced Grant (ERC‐2017‐ADG) (to David H. Rowitch); the German Research Foundation (SCHI 1330/1‐1), the Hertie Foundation (medMS MyLab, P1180016) and the National Multiple Sclerosis Society (FG‐1607‐25111 and FG‐1902‐33617) (to Lucas Schirmer); NIH NINDS (R01NS102156), NMSS research grant (RG‐1701‐26630) and Dana Foundation: The David Mahoney Neuroimaging program (to Myriam M. Chaumeil). Lucile Ben Haim is currently supported by a Fondation pour la Recherche Medicale fellowship (ARF201909009244). NG2‐DsRed Funding Information: Deutsche Forschungsgemeinschaft, Grant/Award Number: SCHI 1330/1‐1 (to L.S.); Fondation pour la Recherche M{\'e}dicale, Grant/Award Number: ARF201909009244 (to L.B.H.); Gemeinn{\"u}tzige Hertie‐Stiftung, Grant/Award Number: medMS MyLab P1180016 (to L.S.); H2020 European Research Council, Grant/Award Number: ERC‐2017‐ADG (to D.H.R.); National Institute of Neurological Disorders and Stroke, Grant/Award Numbers: P01NS083513 (to D.H.R.), R01NS102156 (to M.M.C.); Wellcome Trust, Grant/Award Number: Wellcome Trust Senior Investigator Award (to D.H.R); Dana Foundation, Grant/Award Number: The David Mahoney Neuroimaging program (to M.M.C.); National Multiple Sclerosis Society, Grant/Award Number: RG‐1701‐26630 (to M.M.C.), FG‐1607‐2511 and FG‐1902‐33617 (to L.S.) Funding information Funding Information: We thank Dr. S. Fancy for providing NG2-DsRed mice (originally developed by Dr. A. Nishiyama) and Dr. M. Chavali for technical help. We thank Drs. C. Escartin and C. Lobsiger for inputs on the project, critical reading of the manuscript and feedback on figures. This work was supported by: the Wellcome Trust, NIH NINDS (P01NS083513) and ERC Advanced Grant (ERC-2017-ADG) (to David H. Rowitch); the German Research Foundation (SCHI 1330/1-1), the Hertie Foundation (medMS MyLab, P1180016) and the National Multiple Sclerosis Society (FG-1607-25111 and FG-1902-33617) (to Lucas Schirmer); NIH NINDS (R01NS102156), NMSS research grant (RG-1701-26630) and Dana Foundation: The David Mahoney Neuroimaging program (to Myriam M. Chaumeil). Lucile Ben Haim is currently supported by a Fondation pour la Recherche Medicale fellowship (ARF201909009244). Publisher Copyright: {\textcopyright} 2021 Wiley Periodicals LLC. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = dec,
doi = "10.1002/glia.24071",
language = "English",
volume = "69",
pages = "2812--2827",
journal = "Glia",
issn = "0894-1491",
publisher = "John Wiley and Sons Inc.",
number = "12",
}
SDG 3 Good Health and Well-being