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Dipeptide Mimetic of the Brain-derived Neurotrophic Factor Prevents Impairments of Neurogenesis in Stressed Mice

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Bulletin of Experimental Biology and Medicine Aims and scope

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.

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Authors and Affiliations

  1. Laboratory of Peptide Bioregulators, V. V. Zakusov Research Institute of Pharmacology, Moscow, Russia

    T. A. Gudasheva & P. Yu. Povarnina

  2. Department of Pharmacogenetics, V. V. Zakusov Research Institute of Pharmacology, Moscow, Russia

    S. B. Seredenin

Authors
  1. T. A. Gudasheva
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  2. P. Yu. Povarnina
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  3. S. B. Seredenin
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Correspondence to T. A. Gudasheva.

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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 162, No. 10, pp. 448-451, October, 2016

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Gudasheva, T.A., Povarnina, P.Y. & Seredenin, S.B. Dipeptide Mimetic of the Brain-derived Neurotrophic Factor Prevents Impairments of Neurogenesis in Stressed Mice. Bull Exp Biol Med 162, 454–457 (2017). https://doi.org/10.1007/s10517-017-3638-9

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  • DOI: https://doi.org/10.1007/s10517-017-3638-9

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