Journal Article

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

Vakhitova, Yulia V., Kudryashov, Nikita V., Seredenin, Sergei B., Voronin, Mikhail V., Kalinina, Tatiana S., Lusta, Anastasiya Yu, Volkova, Anna V., Gudasheva, Tatiana A., Kadnikov, Ilya A., Shimshirt, Alexander A., Zainullina, Liana F.

2021

Overview

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.

• Publisher: MDPI AG,MDPI
• Subject: Animals / Antidepressants / Antidepressive Agents - pharmacology / Apoptosis / Behavior / Binding sites / Brain - metabolism / Brain-Derived Neurotrophic Factor - drug effects / Brain-Derived Neurotrophic Factor - metabolism / Chronic illnesses / Dipeptides - metabolism / Dipeptides - pharmacology / Gene expression / Hippocampus - drug effects / Hippocampus - metabolism / Male / Membrane Glycoproteins - drug effects / Membrane Glycoproteins - metabolism / Mental depression / Mice / Mice, Inbred BALB C / Molecular weight / Neurosciences / Pathophysiology / Peptides / Pharmacokinetics / Phosphorylation / Prefrontal Cortex - drug effects / Prefrontal Cortex - metabolism / Protein-Tyrosine Kinases - drug effects / Protein-Tyrosine Kinases - metabolism / Proteins / Serotonin / Signal transduction / Signal Transduction - drug effects / Stress / Stress, Psychological