Ablation of Gabra5 Influences Corticosterone Levels and Anxiety-like Behavior in Mice

• Published in: Genes 2023-01, Vol.14 (2), p.285
• Main Authors: Syding, Linn Amanda, Kubik-Zahorodna, Agnieszka, Reguera, David Pajuelo, Nickl, Petr, Hruskova, Bohdana, Kralikova, Michaela, Kopkanova, Jana, Novosadova, Vendula, Kasparek, Petr, Prochazka, Jan, Rozman, Jan, Turecek, Rostislav, Sedlacek, Radislav
• Format: Article
• Language: English
• Subjects: Ablation; Animals; Anxiety; Anxiety disorders; Behavior; Brain; Corticosterone; Feces; Glucocorticoids; Hippocampus; Humans; Hypothalamic-pituitary-adrenal axis; Hypothalamo-Hypophyseal System - metabolism; Hypothalamus; Metabolites; Mice; Phenotypes; Pituitary; Pituitary-Adrenal System - metabolism; Proteins; Receptors, GABA - metabolism; Receptors, GABA-A - genetics; Receptors, GABA-A - metabolism; Stress response; Testosterone; γ-Aminobutyric acid
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes14020285

Stress responses are activated by the hypothalamic-pituitary-adrenal axis (HPA axis), culminating in the release of glucocorticoids. During prolonged periods of secretion of glucocorticoids or inappropriate behavioral responses to a stressor, pathologic conditions may occur. Increased glucocorticoid concentration is linked to generalized anxiety, and there are knowledge gaps regarding its regulation. It is known that the HPA axis is under GABAergic control, but the contribution of the individual subunits of the GABA receptor is largely unknown. In this study, we investigated the relationship between the α5 subunit and corticosterone levels in a new mouse model deficient for , which is known to be linked to anxiety disorders in humans and phenologs observed in mice. We observed decreased rearing behavior, suggesting lower anxiety in the animals; however, such a phenotype was absent in the open field and elevated plus maze tests. In addition to decreased rearing behavior, we also found decreased levels of fecal corticosterone metabolites in mice indicating a lowered stress response. Moreover, based on the electrophysiological recordings where we observed a hyperpolarized state of hippocampal neurons, we hypothesize that the constitutive ablation of the gene leads to functional compensation with other channels or GABA receptor subunits in this model.