A study on the mnemotropic and antidepressant-like effects of the low-molecular-weight mimetic of nerve growth factor, dipeptide GK-2, in experimental ischemic stroke

Relevance. The nerve growth factor (NGF), possessing neuroprotective and neuroregenerative properties, holds promise for the development of medications for the treatment of post-stroke conditions. At the Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, a...

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Main Authors: P. Yu. Povarnina, N. M. Sazonova, D. M. Nikiforov, T. A. Gudasheva, V. L. Dorofeev
Format: Article
Language:Russian
Published: LLC “Publisher OKI” 2024-06-01
Series:Фармакокинетика и Фармакодинамика
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Online Access:https://www.pharmacokinetica.ru/jour/article/view/406
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author P. Yu. Povarnina
N. M. Sazonova
D. M. Nikiforov
T. A. Gudasheva
V. L. Dorofeev
author_facet P. Yu. Povarnina
N. M. Sazonova
D. M. Nikiforov
T. A. Gudasheva
V. L. Dorofeev
author_sort P. Yu. Povarnina
collection DOAJ
description Relevance. The nerve growth factor (NGF), possessing neuroprotective and neuroregenerative properties, holds promise for the development of medications for the treatment of post-stroke conditions. At the Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, a dimeric dipeptide mimic of NGF with the laboratory code GK-2 was designed and synthesized. Under conditions of experimental cerebral ischemia, it significantly reduced the volume of brain infarction and stimulated neuro- and synaptogenesis.Objective. The aim of this study was to investigate the effects of GK-2 on experimental post-stroke dementia and depression.Methods. Ischemic stroke was induced by occlusion of the middle cerebral artery (MCAO) in Wistar rats. GK-2 was administered intraperitoneally at a dose of 0.5 mg/kg for 21 days post MCAO. Short-term and long-term memory of the animals were assessed 30–40 days post MCAO using the novel object recognition test. Depressive-like state was evaluated through the forced swimming test and sucrose preference test.Results. In animals subjected to MCAO, both short-term and long-term memory exhibited a statistically significant decline of 80 %, along with a depressive-like state characterized by a 50 % increase in total immobility time and a 30 % reduction in sucrose preference, when compared to the sham-lesioned group. Dipeptide GK-2 completely averted the onset of these impairments.Conclusion. The dipeptide mimic of NGF, GK-2, mitigates the development of cognitive and psychomotional impairments in the setting of experimental stroke.
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series Фармакокинетика и Фармакодинамика
spelling doaj-art-abc97dadc5dd418eafc60783841118502025-08-20T03:42:33ZrusLLC “Publisher OKI”Фармакокинетика и Фармакодинамика2587-78362686-88302024-06-0101142210.37489/2587-7836-2024-1-14-22364A study on the mnemotropic and antidepressant-like effects of the low-molecular-weight mimetic of nerve growth factor, dipeptide GK-2, in experimental ischemic strokeP. Yu. Povarnina0N. M. Sazonova1D. M. Nikiforov2T. A. Gudasheva3V. L. Dorofeev4FSBSI «Federal research center for innovator and emerging biomedical and pharmaceutical technologies»FSBSI «Federal research center for innovator and emerging biomedical and pharmaceutical technologies»FSBSI «Federal research center for innovator and emerging biomedical and pharmaceutical technologies»FSBSI «Federal research center for innovator and emerging biomedical and pharmaceutical technologies»FSBSI «Federal research center for innovator and emerging biomedical and pharmaceutical technologies»Relevance. The nerve growth factor (NGF), possessing neuroprotective and neuroregenerative properties, holds promise for the development of medications for the treatment of post-stroke conditions. At the Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies, a dimeric dipeptide mimic of NGF with the laboratory code GK-2 was designed and synthesized. Under conditions of experimental cerebral ischemia, it significantly reduced the volume of brain infarction and stimulated neuro- and synaptogenesis.Objective. The aim of this study was to investigate the effects of GK-2 on experimental post-stroke dementia and depression.Methods. Ischemic stroke was induced by occlusion of the middle cerebral artery (MCAO) in Wistar rats. GK-2 was administered intraperitoneally at a dose of 0.5 mg/kg for 21 days post MCAO. Short-term and long-term memory of the animals were assessed 30–40 days post MCAO using the novel object recognition test. Depressive-like state was evaluated through the forced swimming test and sucrose preference test.Results. In animals subjected to MCAO, both short-term and long-term memory exhibited a statistically significant decline of 80 %, along with a depressive-like state characterized by a 50 % increase in total immobility time and a 30 % reduction in sucrose preference, when compared to the sham-lesioned group. Dipeptide GK-2 completely averted the onset of these impairments.Conclusion. The dipeptide mimic of NGF, GK-2, mitigates the development of cognitive and psychomotional impairments in the setting of experimental stroke.https://www.pharmacokinetica.ru/jour/article/view/406ngfdipeptide mimeticpost-stroke depressionpost-stroke dementia
spellingShingle P. Yu. Povarnina
N. M. Sazonova
D. M. Nikiforov
T. A. Gudasheva
V. L. Dorofeev
A study on the mnemotropic and antidepressant-like effects of the low-molecular-weight mimetic of nerve growth factor, dipeptide GK-2, in experimental ischemic stroke
Фармакокинетика и Фармакодинамика
ngf
dipeptide mimetic
post-stroke depression
post-stroke dementia
title A study on the mnemotropic and antidepressant-like effects of the low-molecular-weight mimetic of nerve growth factor, dipeptide GK-2, in experimental ischemic stroke
title_full A study on the mnemotropic and antidepressant-like effects of the low-molecular-weight mimetic of nerve growth factor, dipeptide GK-2, in experimental ischemic stroke
title_fullStr A study on the mnemotropic and antidepressant-like effects of the low-molecular-weight mimetic of nerve growth factor, dipeptide GK-2, in experimental ischemic stroke
title_full_unstemmed A study on the mnemotropic and antidepressant-like effects of the low-molecular-weight mimetic of nerve growth factor, dipeptide GK-2, in experimental ischemic stroke
title_short A study on the mnemotropic and antidepressant-like effects of the low-molecular-weight mimetic of nerve growth factor, dipeptide GK-2, in experimental ischemic stroke
title_sort study on the mnemotropic and antidepressant like effects of the low molecular weight mimetic of nerve growth factor dipeptide gk 2 in experimental ischemic stroke
topic ngf
dipeptide mimetic
post-stroke depression
post-stroke dementia
url https://www.pharmacokinetica.ru/jour/article/view/406
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