PUBLICATION

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

Authors
Turan, F., Yilmaz, Ö., Schünemann, L., Lindenberg, T.T., Kalanithy, J.C., Harder, A., Ahmadi, S., Duman, T., MacDonald, R.B., Winter, D., Liu, C., Odermatt, B.
ID
ZDB-PUB-210915-6
Date
2021
Source
Journal of neuroscience research   99(11): 2774-2792 (Journal)
Registered Authors
Liu, Changsheng, Odermatt, Benjamin
Keywords
OPC, RRID:AB_476697, glia, glutamate signaling, iGluSnFR, myelin, oligodendrocyte, zebrafish
MeSH Terms
  • Animals
  • Oligodendroglia*/metabolism
  • Female
  • Male
  • Glutamates/metabolism
  • Axons/metabolism
  • Zebrafish*
  • Myelin Sheath/metabolism
(all 8)
PubMed
34520578 Full text @ J. Neurosci. Res.
Abstract
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.
Genes / Markers
Figures
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
cu3313TgTransgenic Insertion
    ue101TgTransgenic Insertion
      vu19TgTransgenic Insertion
        zf167TgTransgenic Insertion
          zf3629TgTransgenic Insertion
            zf3630TgTransgenic Insertion
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              Human Disease / Model
              No data available
              Sequence Targeting Reagents
              No data available
              Fish
              No data available
              Antibodies
              Name Type Antigen Genes Isotypes Host Organism
              Ab4-pcnapolyclonalRabbit
              Ab5-casp3polyclonal
                		Rabbit
                Ab8-mbppolyclonal
                  		IgGRabbit
                  1 - 3 of 3
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                  Orthology
                  No data available
                  Engineered Foreign Genes
                  Marker Marker Type Name
                  cpEGFPEFGcpEGFP
                  DsRed2EFGDsRed2
                  GAL4EFGGAL4
                  GFPEFGGFP
                  TomatoEFGTomato
                  1 - 5 of 5
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                  Mapping
                  No data available
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                  Citation
                  Turan, F., Yilmaz, Ö., Schünemann, L., Lindenberg, T.T., Kalanithy, J.C., Harder, A., Ahmadi, S., Duman, T., MacDonald, R.B., Winter, D., Liu, C., Odermatt, B. (2021) Effect of modulating glutamate signaling on myelinating oligodendrocytes and their development-A study in the zebrafish model. Journal of neuroscience research. 99(11):2774-2792.