Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 24, Pages -Publisher
MDPI
DOI: 10.3390/ijms222413381
Keywords
BDNF; dipeptide mimetics; TrkB signaling; antidepressant; unpredictable chronic mild stress
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The study showed that chronic treatment with GSB-106 has antidepressant-like effects in mice under chronic stress, likely through regulation of BDNF-TrkB signaling.
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 pTrkB(816) 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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