Abstract：
:Brain-derived neurotrophic factor (BDNF) plays the central role in the mechanisms of regulation of neurogenesis and neuroplasticity. Impairment of these mechanisms is considered as one of the main etiological factors of depression. Dimeric dipeptide mimetic of BDNF loop 4 bis-(N-monosuccinyl-l-seryl-l-lysine) hexamethylenediamide (GSB-106) was synthesized at the V. V. Zakusov Research Institute of Pharmacology. In vivo experiments revealed significant antidepressant properties of GSB-106 in doses of 0.1-10 mg/kg (intraperitoneally and orally). Effects of GSB-106 on hippocampal neurogenesis were studied in mice subjected to chronic predator stress. Proliferative activity in the subgranular zone of the dental gyrus was assessed immunohistochemically by Ki-67 expression (a marker of dividing cells). It was found that GSB-106 (10 mg/kg, intraperitoneally, 5 days) completely prevents neurogenesis disturbances in stressed mice. These findings suggest that GSB-106 is a promising candidate for the development of antidepressant agents with BDNF-like mechanism of action.
journal_name
Bull Exp Biol Medjournal_title
Bulletin of experimental biology and medicineauthors
Gudasheva TA,Povarnina PY,Seredenin SBdoi
10.1007/s10517-017-3638-9subject
Has Abstractpub_date
2017-02-01 00:00:00pages
454-457issue
4eissn
0007-4888issn
1573-8221pii
10.1007/s10517-017-3638-9journal_volume
162pub_type
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