Therapeutic Potential of GABAergic Signaling in Myelin Plasticity and Repair.

Daniel Reyes-Haro,Abraham Cisneros-Mejorado,Rogelio O Arellano

doi:10.3389/fcell.2021.662191

Daniel Reyes-Haro, Abraham Cisneros-Mejorado + Show 1 more

Open Access

https://doi.org/10.3389/fcell.2021.662191

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Abstract

Oligodendrocytes (OLs) produce myelin to insulate axons. This accelerates action potential propagation, allowing nerve impulse information to synchronize within complex neuronal ensembles and promoting brain connectivity. Brain plasticity includes myelination, a process that starts early after birth and continues throughout life. Myelin repair, followed by injury or disease, requires new OLs differentiated from a population derived from oligodendrocyte precursor cells (OPCs) that continue to proliferate, migrate and differentiate to preserve and remodel myelin in the adult central nervous system. OPCs represent the largest proliferative neural cell population outside the adult neurogenic niches in the brain. OPCs receive synaptic inputs from glutamatergic and GABAergic neurons throughout neurodevelopment, a unique feature among glial cells. Neuron-glia communication through GABA signaling in OPCs has been shown to play a role in myelin plasticity and repair. In this review we will focus on the molecular and functional properties of GABAA receptors (GABAARs) expressed by OPCs and their potential role in remyelination.

Highlights

The oligodendrocyte precursor cells (OPCs) are a dynamic glial population widely distributed in the central nervous system which differentiate into new oligodendrocytes (OLs) participating in myelin remodeling (Serwanski et al, 2018; Bonetto et al, 2020)
Loss of GABAA receptors (GABAARs)-mediated synaptic input to OPCs by hypoxia seems to promote the proliferation of these cells and a delay in OL maturation resulting in cerebellar white matter (WM) demyelination during the early postnatal stage (Zonouzi et al, 2015)
GABAAR activation is involved in the regulation of proliferation, differentiation, axon-glia recognition and myelination onset (Zonouzi et al, 2015; Arellano et al, 2016; Hamilton et al, 2017)

Summary

Introduction

The oligodendrocyte precursor cells (OPCs) are a dynamic glial population widely distributed in the central nervous system which differentiate into new oligodendrocytes (OLs) participating in myelin remodeling (Serwanski et al, 2018; Bonetto et al, 2020). Potentiation by benzodiazepines supports the involvement of a γ subunit in the conformation of the OL-GABAAR, at least at the neonatal stage, given that these studies were performed in primary cultures of cells isolated from the neonate forebrain (P0– P2) or OLs from the optic nerve at P10–P12 (Arellano et al, 2016).

Results

Conclusion