title: Dipeptide Mimetic of the Brain-derived Neurotrophic Factor Prevents Impairments of Neurogenesis in Stressed Mice.
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.
authors.affiliation: Laboratory of Peptide Bioregulators, V. V. Zakusov Research Institute of Pharmacology, Moscow, Russia. tata-sosnovka@mail.ru.
authors.forename: T A
authors.initials: TA
authors.lastname: Gudasheva
authors.affiliation: Laboratory of Peptide Bioregulators, V. V. Zakusov Research Institute of Pharmacology, Moscow, Russia.
authors.forename: P Yu
authors.initials: PY
authors.lastname: Povarnina
authors.affiliation: Department of Pharmacogenetics, V. V. Zakusov Research Institute of Pharmacology, Moscow, Russia.
authors.forename: S B
authors.initials: SB
authors.lastname: Seredenin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004151:Dipeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D007274:Injections, Intraperitoneal; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000187:drug effects*; D057786:Peptidomimetics / Q000138:chemical synthesis / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D004151:Dipeptides; D019394:Ki-67 Antigen; C498355:Mki67 protein, mouse; D057786:Peptidomimetics
keywords: GCB-106; brain-derived neurotrophic factor; dipeptide mimetics; neurogenesis; stress