@article{868e38922bc14ca18898f3b18a11d715,
title = "Oligodendrocytes Support Neuronal Glutamatergic Transmission via Expression of Glutamine Synthetase",
abstract = "Glutamate has been implicated in a wide range of brain pathologies and is thought to be metabolized via the astrocyte-specific enzyme glutamine synthetase (GS). We show here that oligodendrocytes, the myelinating glia of the central nervous system, also express high levels of GS in caudal regions like the midbrain and the spinal cord. Selective removal of oligodendrocyte GS in mice led to reduced brain glutamate and glutamine levels and impaired glutamatergic synaptic transmission without disrupting myelination. Furthermore, animals lacking oligodendrocyte GS displayed deficits in cocaine-induced locomotor sensitization, a behavior that is dependent on glutamatergic signaling in the midbrain. Thus, oligodendrocytes support glutamatergic transmission through the actions of GS and may represent a therapeutic target for pathological conditions related to brain glutamate dysregulation. Xin et al. show that mature oligodendrocytes, the myelinating cells of the brain, express the glutamine-synthesizing enzyme glutamine synthetase (GS). Oligodendrocyte-specific GS deletion does not impair myelination but disrupts neuronal glutamatergic transmission, thus demonstrating a myelin-independent role for oligodendrocytes in supporting glutamate signaling in the brain.",
keywords = "cocaine, glia, glutamate, glutamine, glutamine synthetase, midbrain, oligodendrocyte, transmission",
author = "Wendy Xin and Mironova, {Yevgeniya A.} and Hui Shen and Marino, {Rosa A.M.} and Ari Waisman and Lamers, {Wouter H.} and Bergles, {Dwight E.} and Antonello Bonci",
note = "Funding Information: The authors would like to thank Raffaello Cimbro at the Johns Hopkins Bayview Immunomics Core (supported by NIAMS grant P30 AR-070254) for assistance with flow cytometry; Dr. LaToya Roker and the Johns Hopkins School of Medicine Microscope Facility for assistance with EM sample processing and imaging; Dr. Francois Vautier, Joni McKenzie, and the NIDA IRP Transgenic Breeding staff for assistance with animal husbandry; Drs. Lindsay De Biase, Richard Roth, and Ayesha Sengupta for helpful discussions and feedback during manuscript writing; and Dr. Gail Seabold for proofreading. This work was supported by the NIDA Intramural Research Program of the NIH and an NSF fellowship (grant 1232825) to W.X.; a fellowship from the National Multiple Sclerosis Society to Y.A.M.; and a grant from the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation to D.E.B. W.X. conceptualized the study. W.X. Y.A.M. H.S. and R.A.M.M. performed experiments. A.W. and W.H.L. contributed transgenic mouse lines. D.E.B. provided reagents and scientific expertise. A.B. provided funding and supervised the study. W.X. wrote the manuscript with input from all authors. The authors declare no competing interests. Funding Information: The authors would like to thank Raffaello Cimbro at the Johns Hopkins Bayview Immunomics Core (supported by NIAMS grant P30 AR-070254 ) for assistance with flow cytometry; Dr. LaToya Roker and the Johns Hopkins School of Medicine Microscope Facility for assistance with EM sample processing and imaging; Dr. Francois Vautier, Joni McKenzie, and the NIDA IRP Transgenic Breeding staff for assistance with animal husbandry; Drs. Lindsay De Biase, Richard Roth, and Ayesha Sengupta for helpful discussions and feedback during manuscript writing; and Dr. Gail Seabold for proofreading. This work was supported by the NIDA Intramural Research Program of the NIH and an NSF fellowship (grant 1232825 ) to W.X.; a fellowship from the National Multiple Sclerosis Society to Y.A.M.; and a grant from the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation to D.E.B. Funding Information: The authors would like to thank Raffaello Cimbro at the Johns Hopkins Bayview Immunomics Core (supported by NIAMS grant P30 AR-070254)for assistance with flow cytometry; Dr. LaToya Roker and the Johns Hopkins School of Medicine Microscope Facility for assistance with EM sample processing and imaging; Dr. Francois Vautier, Joni McKenzie, and the NIDA IRP Transgenic Breeding staff for assistance with animal husbandry; Drs. Lindsay De Biase, Richard Roth, and Ayesha Sengupta for helpful discussions and feedback during manuscript writing; and Dr. Gail Seabold for proofreading. This work was supported by the NIDA Intramural Research Program of the NIH and an NSF fellowship (grant 1232825)to W.X.; a fellowship from the National Multiple Sclerosis Society to Y.A.M.; and a grant from the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation to D.E.B. W.X. conceptualized the study. W.X. Y.A.M. H.S. and R.A.M.M. performed experiments. A.W. and W.H.L. contributed transgenic mouse lines. D.E.B. provided reagents and scientific expertise. A.B. provided funding and supervised the study. W.X. wrote the manuscript with input from all authors. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2019 The Authors",
year = "2019",
month = may,
day = "21",
doi = "10.1016/j.celrep.2019.04.094",
language = "English (US)",
volume = "27",
pages = "2262--2271.e5",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "8",
}