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

0570587 - ÚMG 2024 RIV CH eng J - Journal Article
Syding, Linn Amanda - Kubik-Zahorodna, Agnieszka - Reguera, David Pajuelo - Nickl, Petr - Hrušková, Bohdana - Králíková, Michaela - Kopkanová, Jana - Novosadová, Vendula - Kašpárek, Petr - Procházka, Jan - Rozman, Jan - Tureček, Rostislav - Sedláček, Radislav
Ablation of Gabra5 Influences Corticosterone Levels and Anxiety-like Behavior in Mice.
Genes. Roč. 14, č. 2 (2023), č. článku 285. E-ISSN 2073-4425
R&D Projects: GA MŠMT(CZ) LM2018126; GA MŠMT EF16_013/0001789; GA MŠMT EF18_046/0015861; GA MŠMT ED2.1.00/19.0395; GA ČR(CZ) GA19-09283S
EU Projects: European Commission(XE) 765269 - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
Grant - others:AV ČR(CZ) StrategieAV21/29
Program: StrategieAV
Institutional support: RVO:68378041 ; RVO:68378050
Keywords : corticosterone * GABA receptor * anxiety * behavior * mouse model
OECD category: Technologies involving identifying the functioning of DNA, proteins and enzymes and how they influence the onset of disease and maintenance of well-being (gene-based diagnostics and therapeutic interventions (pharmacogenomics, gene-based therapeutics); Neurosciences (including psychophysiology (UEM-P)
Impact factor: 3.5, year: 2022
Method of publishing: Open access
https://www.mdpi.com/2073-4425/14/2/285

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 alpha 5 subunit and corticosterone levels in a new mouse model deficient for Gabra5, 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 Gabra5(-/-) 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 Gabra5(-/-) 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 Gabra5 gene leads to functional compensation with other channels or GABA receptor subunits in this model.
Permanent Link: https://hdl.handle.net/11104/0341891