Abstract
Myelin facilitates the fast transmission of nerve impulses and provides metabolic support to axons. Differentiation of oligodendrocyte progenitor cells (OPCs) and Schwann cell (SC) precursors is critical for myelination during development and myelin repair in demyelinating disorders. Myelination is tightly controlled by neuron-glia communication and requires the participation of a wide repertoire of signals, including neurotransmitters such as glutamate, ATP, adenosine, or γ-aminobutyric acid (GABA). GABA is the main inhibitory neurotransmitter in the central nervous system (CNS) and it is also present in the peripheral nervous system (PNS). The composition and function of GABA receptors (GABARs) are well studied in neurons, while their nature and role in glial cells are still incipient. Recent studies demonstrate that GABA-mediated signaling mechanisms play relevant roles in OPC and SC precursor development and function, and stand out the implication of GABARs in oligodendrocyte (OL) and SC maturation and myelination. In this review, we highlight the evidence supporting the novel role of GABA with an emphasis on the molecular identity of the receptors expressed in these glial cells and the possible signaling pathways involved in their actions. GABAergic signaling in myelinating cells may have potential implications for developing novel reparative therapies in demyelinating diseases.
Highlights
Glial cells express a vast repertoire of receptors and transporters for neurotransmitters and neuromodulators and respond to axonal signals, being key and active elements of the nervous system (Allen and Lyons, 2018)
GABA is among the signals that drive OLs and Schwann cell (SC) to axon interactions
The fact that GABA acts mainly on two different types of receptors—ionotropic GABAARs and metabotropic GABAB receptors (GABABRs)—makes it difficult to understand the role of this neurotransmitter in myelinating cell physiology
Summary
Reviewed by: Åsa Fex-Svenningsen, University of Southern Denmark, Denmark Beatriz Garcia-Diaz, INSERM U1127 Institut du Cerveau et de la Moelle épinière (ICM), France Maria Cecilia Angulo, Centre National de la Recherche Scientifique (CNRS), France. Differentiation of oligodendrocyte progenitor cells (OPCs) and Schwann cell (SC) precursors is critical for myelination during development and myelin repair in demyelinating disorders. The composition and function of GABA receptors (GABARs) are well studied in neurons, while their nature and role in glial cells are still incipient. Recent studies demonstrate that GABA-mediated signaling mechanisms play relevant roles in OPC and SC precursor development and function, and stand out the implication of GABARs in oligodendrocyte (OL) and SC maturation and myelination. We highlight the evidence supporting the novel role of GABA with an emphasis on the molecular identity of the receptors expressed in these glial cells and the possible signaling pathways involved in their actions. GABAergic signaling in myelinating cells may have potential implications for developing novel reparative therapies in demyelinating diseases
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