Gabra5, encoding the α5 subunit of the GABAA receptor, is a crucial gene in the central nervous system. GABAA receptors are ligand-gated chloride channels that mediate inhibitory neurotransmission, thus regulating various neural activities. This gene is involved in pathways related to the hypothalamic-pituitary-adrenal axis regulation, energy balance, and neuronal excitability-inhibition balance [3,4].

In mouse models, gene-specific knock-down of Gabra5 in mature hypothalamic POMC neurons led to sexually dimorphic effects. In male mice, it increased the firing frequency and resting membrane potential of POMC neurons, improved glucose tolerance, while in female mice, only a modest decrease in the frequency of miniature inhibitory postsynaptic current was observed [2]. Ablation of Gabra5 in mice decreased rearing behavior and fecal corticosterone metabolites, suggesting lower anxiety and stress response, potentially due to functional compensation with other channels or GABA receptor subunits [4]. In diet-induced obesity mouse models, chemogenetic inhibition of GABRA5-positive neurons in the lateral hypothalamic area (LHA) suppressed fat thermogenesis and increased weight gain, while gene silencing of Gabra5 in LHA decreased weight gain [1].

In conclusion, Gabra5 plays significant roles in regulating energy balance, glucose metabolism, stress response, and anxiety-like behavior. Mouse models with gene knockout or knockdown of Gabra5 have provided valuable insights into its functions in these physiological processes, highlighting its potential as a therapeutic target for obesity, glucose metabolism disorders, and anxiety-related diseases.