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Protective effects of VMY-2-95 on corticosterone-induced injuries in mice and cellular models

Nicotinic α4β2 receptor antagonists have drawn increasing attention in the development of new antidepressants. In this study, we aimed to investigate the protective effect of VMY-2-95, the new selective antagonist of α4β2 nicotinic acetylcholine receptor (nAChR) on corticosterone (CORT) injured mice...

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Autores principales: Yu, Ziru, Kong, Dewen, Liang, Yu, Zhao, Xiaoyue, Du, Guanhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343195/
https://www.ncbi.nlm.nih.gov/pubmed/34386327
http://dx.doi.org/10.1016/j.apsb.2021.03.002
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author Yu, Ziru
Kong, Dewen
Liang, Yu
Zhao, Xiaoyue
Du, Guanhua
author_facet Yu, Ziru
Kong, Dewen
Liang, Yu
Zhao, Xiaoyue
Du, Guanhua
author_sort Yu, Ziru
collection PubMed
description Nicotinic α4β2 receptor antagonists have drawn increasing attention in the development of new antidepressants. In this study, we aimed to investigate the protective effect of VMY-2-95, the new selective antagonist of α4β2 nicotinic acetylcholine receptor (nAChR) on corticosterone (CORT) injured mice and cellular models. Fluoxetine was applied as a positive control, and the effects of VMY-2-95 were investigated with three different doses or concentrations (1, 3, 10 mg/kg in mice, and 0.003, 0.03, 0.1 μmol/L in cells). As a result, VMY-2-95 showed significant antidepressant-like effects in the CORT injured mice by improving neuromorphic function, promoting hippocampal nerve proliferation, and regulating the contents of monoamine transmitters. Meanwhile, VMY-2-95 exhibited protective effects on cell viability, cell oxidant, cell apoptosis, and mitochondrial energy metabolism on corticosterone-impaired SH-SY5Y cells. Also, the PKA–CREB–BDNF signaling pathway was up-regulated by VMY-2-95 both in vitro and in vivo, and pathway blockers were also combined with VMY-2-95 to verify the effects furtherly. Therefore, we preliminarily proved that VMY-2-95 had protective effects in depressed mice and SH-SY5Y cells against injuries induced by corticosterone. This work indicated that the application of VMY-2-95 is a potential pharmacological solution for depression. This study also supported the development of α4β2 nAChR antagonists towards neuropsychiatric dysfunctions.
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spelling pubmed-83431952021-08-11 Protective effects of VMY-2-95 on corticosterone-induced injuries in mice and cellular models Yu, Ziru Kong, Dewen Liang, Yu Zhao, Xiaoyue Du, Guanhua Acta Pharm Sin B Original Article Nicotinic α4β2 receptor antagonists have drawn increasing attention in the development of new antidepressants. In this study, we aimed to investigate the protective effect of VMY-2-95, the new selective antagonist of α4β2 nicotinic acetylcholine receptor (nAChR) on corticosterone (CORT) injured mice and cellular models. Fluoxetine was applied as a positive control, and the effects of VMY-2-95 were investigated with three different doses or concentrations (1, 3, 10 mg/kg in mice, and 0.003, 0.03, 0.1 μmol/L in cells). As a result, VMY-2-95 showed significant antidepressant-like effects in the CORT injured mice by improving neuromorphic function, promoting hippocampal nerve proliferation, and regulating the contents of monoamine transmitters. Meanwhile, VMY-2-95 exhibited protective effects on cell viability, cell oxidant, cell apoptosis, and mitochondrial energy metabolism on corticosterone-impaired SH-SY5Y cells. Also, the PKA–CREB–BDNF signaling pathway was up-regulated by VMY-2-95 both in vitro and in vivo, and pathway blockers were also combined with VMY-2-95 to verify the effects furtherly. Therefore, we preliminarily proved that VMY-2-95 had protective effects in depressed mice and SH-SY5Y cells against injuries induced by corticosterone. This work indicated that the application of VMY-2-95 is a potential pharmacological solution for depression. This study also supported the development of α4β2 nAChR antagonists towards neuropsychiatric dysfunctions. Elsevier 2021-07 2021-03-09 /pmc/articles/PMC8343195/ /pubmed/34386327 http://dx.doi.org/10.1016/j.apsb.2021.03.002 Text en © 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original Article
Yu, Ziru
Kong, Dewen
Liang, Yu
Zhao, Xiaoyue
Du, Guanhua
Protective effects of VMY-2-95 on corticosterone-induced injuries in mice and cellular models
title Protective effects of VMY-2-95 on corticosterone-induced injuries in mice and cellular models
title_full Protective effects of VMY-2-95 on corticosterone-induced injuries in mice and cellular models
title_fullStr Protective effects of VMY-2-95 on corticosterone-induced injuries in mice and cellular models
title_full_unstemmed Protective effects of VMY-2-95 on corticosterone-induced injuries in mice and cellular models
title_short Protective effects of VMY-2-95 on corticosterone-induced injuries in mice and cellular models
title_sort protective effects of vmy-2-95 on corticosterone-induced injuries in mice and cellular models
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343195/
https://www.ncbi.nlm.nih.gov/pubmed/34386327
http://dx.doi.org/10.1016/j.apsb.2021.03.002
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