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Ablation of Gabra5 Influences Corticosterone Levels and Anxiety-like Behavior in Mice
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SYSNO ASEP 0570587 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Ablation of Gabra5 Influences Corticosterone Levels and Anxiety-like Behavior in Mice Author(s) Syding, Linn Amanda (UMG-J)
Kubik-Zahorodna, Agnieszka (UMG-J)
Reguera, David Pajuelo (UMG-J)
Nickl, Petr (UMG-J)
Hrušková, Bohdana (UEM-P)
Králíková, Michaela (UEM-P) RID
Kopkanová, Jana (UMG-J)
Novosadová, Vendula (UMG-J)
Kašpárek, Petr (UMG-J)
Procházka, Jan (UMG-J) ORCID
Rozman, Jan (UMG-J)
Tureček, Rostislav (UEM-P) RID, ORCID
Sedláček, Radislav (UMG-J) RIDNumber of authors 13 Article number 285 Source Title Genes. - : MDPI
Roč. 14, č. 2 (2023)Number of pages 17 s. Language eng - English Country CH - Switzerland 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) R&D Projects LM2018126 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) EF16_013/0001789 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) EF18_046/0015861 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED2.1.00/19.0395 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) GA19-09283S GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support UEM-P - RVO:68378041 ; UMG-J - RVO:68378050 UT WOS 000939150000001 EID SCOPUS 85148851104 DOI 10.3390/genes14020285 Annotation 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. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2024 Electronic address https://www.mdpi.com/2073-4425/14/2/285
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