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.
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http://dx.doi.org/10.3389/fncel.2020.00256 | DOI Listing |
Protein Sci
January 2025
Department of Neuroscience, Biomedicine and Movement Sciences, Section of Biochemistry, University of Verona, Verona, Italy.
Human succinic semialdehyde dehydrogenase is a mitochondrial enzyme fundamental in the neurotransmitter γ-aminobutyric acid catabolism. It catalyzes the NAD-dependent oxidative degradation of its derivative, succinic semialdehyde, to succinic acid. Mutations in its gene lead to an inherited neurometabolic rare disease, succinic semialdehyde dehydrogenase deficiency, characterized by mental and developmental delay.
View Article and Find Full Text PDFZh Nevrol Psikhiatr Im S S Korsakova
December 2024
Research Center of Neurology, Moscow, Russia.
At the present stage, great progress has been achieved in understanding the mechanisms of the development of cerebral ischemia. This became possible due to the achievements of theoretical disciplines, in connection with which the general biological approach was formed in the study of pathogenesis of acute and chronic cerebrovascular disorders (CVD). The discovery of pathways of free radical oxidation in cerebral ischemia made it possible to substantiate and develop therapeutic strategies using drugs with antioxidant and neuroprotective activity.
View Article and Find Full Text PDFCell Biochem Biophys
December 2024
Research Center of Neurology, Moscow, Russia.
Allopregnanolone (Allo) is a positive allosteric modulator of the GABA receptor, and amiloride (Ami) is a competitive antagonist of the GABA receptor. The purpose of this work was to study the combined effect of Allo and Ami on functional activity of GABA receptor. The GABA-induced chloride current (I) was measured in isolated Purkinje cells of rat cerebellum using the patch-clamp technique and a system of fast application.
View Article and Find Full Text PDFProg Neurobiol
December 2024
Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, PR China. Electronic address:
In response to stressors, individuals manifest varied behavioral responses directed toward satisfying physiological survival needs. Although the enduring effects of adolescent stress on both humans and animals are well-documented, the underlying mechanisms remain insufficiently elucidated. Utilizing immunofluorescence, viral injections, and brain slice electrophysiological recordings, we have delineated that heightened excitability among glutamatergic neurons in the basolateral amygdala (BLA) is responsible for inducing heightened exploratory behaviors in adolescent mice subjected to mild, chronic restraint stress.
View Article and Find Full Text PDFPLoS Comput Biol
December 2024
Krembil Centre for Neuroinformatics, Centre for Addiction and Mental Health, Toronto, Canada.
Treatment for major depressive disorder (depression) often has partial efficacy and a large portion of patients are treatment resistant. Recent studies implicate reduced somatostatin (SST) interneuron inhibition in depression, and new pharmacology boosting this inhibition via positive allosteric modulators of α5-GABAA receptors (α5-PAM) offers a promising effective treatment. However, testing the effect of α5-PAM on human brain activity is limited, meriting the use of detailed simulations.
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