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Evidence for glutamine synthetase function in mouse spinal cord oligodendrocytes

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 oligoden...

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Main Authors: Ben Haim, Lucile (Author) , Schirmer, Lucas (Author) , Zulji, Amel (Author) , Sabeur, Khalida (Author) , Tiret, Brice (Author) , Ribon, Matthieu (Author) , Chang, Sandra (Author) , Lamers, Wouter H. (Author) , Boillée, Séverine (Author) , Chaumeil, Myriam M. (Author) , Rowitch, David H. (Author)
Format: Article (Journal)
Language:English
Published: 15 August 2021
In: Glia
Year: 2021, Volume: 69, Issue: 12, Pages: 2812-2827
ISSN:1098-1136
DOI:10.1002/glia.24071
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/glia.24071
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/glia.24071
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Author Notes:Lucile Ben Haim, Lucas Schirmer, Amel Zulji, Khalida Sabeur, Brice Tiret, Matthieu Ribon, Sandra Chang, Wouter H. Lamers, Séverine Boillée, Myriam M. Chaumeil, David H. Rowitch
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Summary: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.
Item Description:First Published: 15 August 2021
Gesehen am 13.12.2022
Physical Description:Online Resource
ISSN:1098-1136
DOI:10.1002/glia.24071

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