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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Research Article

Сhronically Administered BDNF Dipeptide Mimetic GSB-106 Prevents the Depressive-like Behavior and Memory Impairments after Transient Middle Cerebral Artery Occlusion in Rats

Author(s): Polina Y. Povarnina, Tatyana A. Antipova, Ilya O. Logvinov, Tatiana A. Gudasheva* and Sergey B. Seredenin

Volume 29, Issue 2, 2023

Published on: 13 January, 2023

Page: [126 - 132] Pages: 7

DOI: 10.2174/1381612829666230103161824

Price: $65

Abstract

Background: A dipeptide mimetic of the BDNF loop 4, bis (N-monosuccinyl-L-seryl-L-lysine) hexamethylenediamide, GSB-106, was designed and synthesized by V.V. Zakusov Research Institute of Pharmacology. The compound activated in vitro TrkB, MAPK/ERK, PI3K/AKT, and PLCγ, like full-length BDNF. In vivo, GSB-106 exhibited antidepressant-like, neuroprotective and neuroregenerative properties. The aim of this work was to study the effects of GSB-106 on depressive-like behavior, cognitive impairments, as well as on hippocampal neuroplasticity in an experimental model of ischemic stroke.

Methods: Male Wistar rats were subjected to 60 minutes of transient middle cerebral artery occlusion (MCAO). Dipeptide GSB-106 was administered intraperitoneally at a dose of 0.1 mg/kg/day for 21 days after surgery. 30-40 days after MCAO, the depressive-like state in the forced swimming test and memory impairment in the novel object recognition test were assessed. Then, the content of CREB, as a neuroplasticity marker, was assessed in the ipsilateral hippocampus.

Results: Rats in MCAO group showed depression-like behavior (increase in immobility time in the forced swimming test by 22% compared to sham group), impairments in short-term and long-term memory (decrease in the discrimination index in the novel object recognition test by 70% and 50%, respectively), and a decrease in immunoreactivity to CREB (cAMP response element-binding protein) in the hippocampus by 36% as compared with the sham group. GSB-106 completely prevented the behavior impairments and counteracted the reduction of immunoreactivity to CREB in the hippocampus.

Conclusion: The BDNF dipeptide mimetic GSB-106 is promising for further development as a drug for the treatment of poststroke neuropsychiatric disorders.

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