Analysis of Antidepressant-like Effects and Action Mechanisms of GSB-106, a Small Molecule, Affecting the TrkB Signaling

Autor:	Yulia V. Vakhitova, Tatiana S. Kalinina, Liana F. Zainullina, Anastasiya Yu. Lusta, Anna V. Volkova, Nikita V. Kudryashov, Tatiana A. Gudasheva, Alexander A. Shimshirt, Ilya A. Kadnikov, Mikhail V. Voronin, Sergei B. Seredenin
Rok vydání:	2021
Předmět:	Male QH301-705.5 Prefrontal Cortex Hippocampus Article Catalysis Inorganic Chemistry Mice BDNF dipeptide mimetics TrkB signaling antidepressant unpredictable chronic mild stress Animals Biology (General) Physical and Theoretical Chemistry QD1-999 Molecular Biology Spectroscopy Mice Inbred BALB C Membrane Glycoproteins Brain-Derived Neurotrophic Factor Organic Chemistry Brain Dipeptides General Medicine Protein-Tyrosine Kinases Antidepressive Agents Computer Science Applications Chemistry Stress Psychological Signal Transduction
Zdroj:	International Journal of Molecular Sciences, Vol 22, Iss 13381, p 13381 (2021) International Journal of Molecular Sciences; Volume 22; Issue 24; Pages: 13381 International Journal of Molecular Sciences
ISSN:	1422-0067
DOI:	10.3390/ijms222413381
Popis:	Induction of BDNF-TrkB signaling is associated with the action mechanisms of conventional and fast-acting antidepressants. GSB-106, developed as a small dimeric dipeptide mimetic of BDNF, was previously shown to produce antidepressant-like effects in the mouse Porsolt test, tail suspension test, Nomura water wheel test, in the chronic social defeat stress model and in the inflammation-induced model of depression. In the present study, we evaluated the effect of chronic per os administration of GSB-106 to Balb/c mice under unpredictable chronic mild stress (UCMS). It was observed for the first time that long term GSB-106 treatment (1 mg/kg, 26 days) during ongoing UCMS procedure ameliorated the depressive-like behaviors in mice as indicated by the Porsolt test. In addition, chronic per os administration of GSB-106 resulted in an increase in BDNF levels, which were found to be decreased in the prefrontal cortex and hippocampus of mice after UCMS. Furthermore, prolonged GSB-106 treatment was accompanied by an increase in the content of pTrkB706/707 in the prefrontal cortex and by a pronounced increase in the level of pTrkB816 in both studied brain structures of mice subjected to UCMS procedure. In summary, the present data show that chronic GSB-106 treatment produces an antidepressant-like effect in the unpredictable chronic mild stress model, which is likely to be associated with the regulation of the BDNF-TrkB signaling.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f7ef8b45af426ca291bee7f78675dd4e https://doi.org/10.3390/ijms222413381 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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