Analysis of Antidepressant-like Effects and Action Mechanisms of GSB-106, a Small Molecule,Affecting the TrkB Signaling |
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Authors: | 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 |
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Affiliation: | 1.Department of Pharmacogenetics, FSBI “Zakusov Institute of Pharmacology”, Baltiyskaya Street 8, 125315 Moscow, Russia; (L.F.Z.); (A.Y.L.); (I.A.K.); (M.V.V.); (S.B.S.);2.Department of Psychopharmacology, FSBI “Zakusov Institute of Pharmacology”, Baltiyskaya Street 8, 125315 Moscow, Russia; (A.V.V.); (N.V.K.); (A.A.S.);3.Department of Medicinal Chemistry, FSBI “Zakusov Institute of Pharmacology”, Baltiyskaya Street 8, 125315 Moscow, Russia; |
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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 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. |
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Keywords: | BDNF dipeptide mimetics TrkB signaling antidepressant unpredictable chronic mild stress |
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