Effect of modulating glutamate signaling on myelinating oligodendrocytes and their development—A study in the zebrafish model

Effect of modulating glutamate signaling on myelinating oligodendrocytes and their development—A study in the zebrafish model

Myelination is crucial for the development and maintenance of axonal integrity, especially fast axonal action potential conduction. There is increasing evidence that glutamate signaling and release through neuronal activity modulates the myelination process. In this study, we examine the effect of m...

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Bibliographic Details
Published in:Journal of neuroscience research Vol. 99; no. 11; pp. 2774 - 2792
Main Authors: Turan, Funda, Yilmaz, Öznur, Schünemann, Lena, Lindenberg, Tobias T., Kalanithy, Jeshurun C., Harder, Alexander, Ahmadi, Shiva, Duman, Türker, MacDonald, Ryan B., Winter, Dominic, Liu, Changsheng, Odermatt, Benjamin
Format: Journal Article
Language:English
Published: United States Wiley Subscription Services, Inc 01-11-2021
Subjects:
Action potential
Animals
Axonogenesis
Axons - metabolism
Cell number
Danio rerio
Demyelinating diseases
Demyelination
Female
Fluorescence
Genes
glia
glutamate signaling
Glutamates - metabolism
Glutamic acid receptors
iGluSnFR
Larvae
Male
Myelin
Myelin Sheath - metabolism
Myelination
oligodendrocyte
Oligodendrocytes
Oligodendroglia - metabolism
OPC
Pyrrolidine
Pyruvic acid
RRID:AB_476697
Signaling
Transaminase
Ventricle
Ventricles (cerebral)
Zebrafish
glutamate signaling
myelin
OPC
iGluSnFR
oligodendrocyte
RRID:AB_476697
zebrafish
glia
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Summary:Myelination is crucial for the development and maintenance of axonal integrity, especially fast axonal action potential conduction. There is increasing evidence that glutamate signaling and release through neuronal activity modulates the myelination process. In this study, we examine the effect of manipulating glutamate signaling on myelination of oligodendrocyte (OL) lineage cells and their development in zebrafish (zf). We use the “intensity‐based glutamate‐sensing fluorescent reporter” (iGluSnFR) in the zf model (both sexes) to address the hypothesis that glutamate is implicated in regulation of myelinating OLs. Our results show that glial iGluSnFR expression significantly reduces OL lineage cell number and the expression of myelin markers in larvae (zfl) and adult brains. The specific glutamate receptor agonist, L‐AP4, rescues this iGluSnFR effect by significantly increasing the expression of the myelin‐related genes, plp1b and mbpa, and enhances myelination in L‐AP4‐injected zfl compared to controls. Furthermore, we demonstrate that degrading glutamate using Glutamat‐Pyruvate Transaminase (GPT) or the blockade of glutamate reuptake by L‐trans‐pyrrolidine‐2,4‐dicarboxylate (PDC) significantly decreases myelin‐related genes and drastically declines myelination in brain ventricle‐injected zfl. Moreover, we found that myelin‐specific ClaudinK (CldnK) and 36K protein expression is significantly decreased in iGluSnFR‐expressing zfl and adult brains compared to controls. Taken together, this study confirms that glutamate signaling is directly required for the preservation of myelinating OLs and for the myelination process itself. These findings further suggest that glutamate signaling may provide novel targets to therapeutically boost remyelination in several demyelinating diseases of the CNS.
Bibliography:Funding information
This work was supported by a NRW‐Repatriation grant to B.O. and by the German Research Foundation (DFG)/(INST 1172/37‐1 FUGG)
Edited by Cristina Ghiani. Reviewed by Marcel Tawk, Joshua Bonkowsky, and Mengsheng Qiu.
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SourceType-Scholarly Journals-1
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ISSN:0360-4012
1097-4547
DOI:10.1002/jnr.24940