Dipeptide BDNF mimetic GSB-106 prevents depression-like behavior and cognitive impairment caused by ischemic stroke in rats


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Relevance. Depression and cognitive impairment are common complications of acute cerebrovascular accidents. Disorders of hippocampal neuroplasticity associated with a decrease in BDNF expression are considered as one of the causes of these complications. A dimeric dipeptide mimetic of the BDNF loop 4, (bis (N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide) (GSB-106) was created at the V.V. Zakusov Research Institute of Pharmacology. GSB-106 demonstrated antidepressant, neuroprotective and neuroregenera-tive properties in in vivo experiments. Objective. Experiments were performed on 40 male rats Wistar weighing 240-280 g. Purpose of the study is to investigate the effect of GSB-106 on depression-like behavior and memory impairments in rats induced by middle cerebral artery occlusion (MCAO). Material and methods. GSB-106 was injected intraperitoneally at a dose of 0.1 mg/kg for 21 days after surgery. Depressive-like be havior was detected in the forced swimming test, and memory impairments - in the novel object recognition test. Conclusions. GSB-106 is a promising compound for further development as a drug for the treatment of post-stroke depression and cognitive impairment.

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作者简介

P. Povarnina

FSBI «Zakusov Institute of Pharmacology»

Email: povarnina@gmail.com

Ph.D. (Biol.)

Moscow, Russia

D. Nikiforov

FSBI «Zakusov Institute of Pharmacology»

Email: povarnina@gmail.com

Ph.D. (Biol.)

Moscow, Russia

O. Vorontsova

FSBI «Zakusov Institute of Pharmacology»

Email: povarnina@gmail.com

Ph.D. (Biol.)

Moscow, Russia

T. Gudasheva

FSBI «Zakusov Institute of Pharmacology»

编辑信件的主要联系方式.
Email: povarnina@gmail.com

Ph.D. (Biol.), Professor, Member-corr. of RAS

Moscow, Russia

参考

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2. Fig. 1. Effect of GSB-106 on depressive-like behavior of rats after OSMA in the forced swimming test: * p<0.05 compared to the "L.O." group; # p<0.05 compared to the "OSMA" group (ANOVA, post hoc Tukey test)

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3. Fig. 2. The effect of GSB-106 on short-term memory of rats after OSMA in the new object recognition test. The test was performed on the 32nd day after surgery, 1 hour after the familiarization phase: ** - p<0.01 compared to the "L.O." group; *** - p<0.0001 compared to the "OSMA" group (ANOVA and post hoc Tukey test)

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4. Fig. 3. The effect of GSB-106 on the long-term memory of rats after OSMA in the new object recognition test. The test was performed on the 33rd day after surgery, 24 hours after the familiarization phase: ** - p<0.01 compared to the "L.O." group; *** - p<0.0001 compared to the "OSMA" group (ANOVA and post hoc Tukey test)

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