Transcriptional and bioinformatic analysis of GABA receptors expressed in oligodendrocyte progenitor cells from the human brain.

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 receptors (GABARs). The molecular identity of GABARs 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 GABARs 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 GABARs 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 GABARs in OPCs. Importantly, we also found a strong correlation between GABAR subunits and transcripts for postsynaptic scaffold proteins, suggesting the potential postsynaptic clustering of GABARs in OPCs.

DISCUSSION

This study presents the first transcriptional-level identification of GABAR subunits expressed in human OPCs, providing potential receptor combinations. Understanding the molecular composition of GABARs 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.