1. Analysis of Antidepressant-like Effects and Action Mechanisms of GSB-106, a Small Molecule, Affecting the TrkB Signaling.
- Author
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Vakhitova YV, Kalinina TS, Zainullina LF, Lusta AY, Volkova AV, Kudryashov NV, Gudasheva TA, Shimshirt AA, Kadnikov IA, Voronin MV, and Seredenin SB
- Subjects
- Animals, Antidepressive Agents pharmacology, Brain metabolism, Brain-Derived Neurotrophic Factor drug effects, Brain-Derived Neurotrophic Factor metabolism, Hippocampus drug effects, Hippocampus metabolism, Male, Membrane Glycoproteins drug effects, Mice, Mice, Inbred BALB C, Prefrontal Cortex drug effects, Prefrontal Cortex metabolism, Protein-Tyrosine Kinases drug effects, Signal Transduction drug effects, Stress, Psychological, Dipeptides metabolism, Dipeptides pharmacology, Membrane Glycoproteins metabolism, Protein-Tyrosine Kinases metabolism
- Abstract
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 pTrkB
706/707 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.- Published
- 2021
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