Abstract
INTRODUCTION: Oligodendrocyte progenitor cells (OPCs) are vital for neuronal myelination and remyelination in the central nervous system. While the molecular mechanisms involved in OPCs' differentiation and maturation are not completely understood, GABA is known to positively influence these processes through the activation of GABA(A) receptors (GABA(A)Rs). The molecular identity of GABA(A)Rs expressed in human OPCs remains unknown, which restricts their specific pharmacological modulation to directly assess their role in oligodendrocytes' maturation and remyelination. METHODS: In this study, we conducted a transcriptomic analysis to investigate the molecular stoichiometry of GABA(A)Rs in OPCs from the human brain. Using eight available transcriptomic datasets from the human brain cortex of control individuals, we analyzed the mRNA expression of all 19 known GABA(A)Rs subunit genes in OPCs, with variations observed across different ages. RESULTS: Our analysis indicated that the most expressed subunits in OPCs are α1-3, β1-3, γ1-3, and ε. Moreover, we determined that the combination of any α with β2 and γ2 is likely to form heteropentameric GABA(A)Rs in OPCs. Importantly, we also found a strong correlation between GABA(A)R subunits and transcripts for postsynaptic scaffold proteins, suggesting the potential postsynaptic clustering of GABA(A)Rs in OPCs. DISCUSSION: This study presents the first transcriptional-level identification of GABA(A)R subunits expressed in human OPCs, providing potential receptor combinations. Understanding the molecular composition of GABA(A)Rs in OPCs not only enhances our knowledge of the underlying mechanisms in oligodendrocyte maturation but also opens avenues for targeted pharmacological interventions aimed at modulating these receptors to promote remyelination in neurological disorders.