Nicotinicα4β2 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 ofα4...Nicotinicα4β2 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 ofα4β2 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 0.003,0.03,0.1μmol/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-SY5 Y 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-SY5 Y 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 ofα4β2 nAChR antagonists towards neuropsychiatric dysfunctions.展开更多
The authors regret that there was a picture error in Fig.5F owing to the inappropriate data statistics—forgetting gating when data collecting and a picture error in Fig.6F owing to the data copy mistake when drawing ...The authors regret that there was a picture error in Fig.5F owing to the inappropriate data statistics—forgetting gating when data collecting and a picture error in Fig.6F owing to the data copy mistake when drawing the column chart.The revisions cause some changes with the data value.展开更多
The authors regret that there was a picture error in the Fig.6D1 owing to the image copy mistake of group-CORT when combining the images of different groups.The revision will cause no change with the data value in Fig...The authors regret that there was a picture error in the Fig.6D1 owing to the image copy mistake of group-CORT when combining the images of different groups.The revision will cause no change with the data value in Fig.6D2,and also do not affect any conclusions of the current work and the description of the whole article.The authors have provided the original data of this figure to Editorial Office,and the corresponding authors or the Editorial Office can be contacted for original data access.展开更多
基金supported by the National Natural Science Foundation of China(No.81603100)the Drug Innovation Major Project(2018ZX09711001-003-005,2018ZX09711001-012,China)+1 种基金CAMS Innovation Fund for Medical Sciences(2017-I2M1-010,China)Peking Union Medical College Graduate Innovation Fund Project(2017-1007-11,China)
文摘Nicotinicα4β2 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 ofα4β2 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 0.003,0.03,0.1μmol/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-SY5 Y 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-SY5 Y 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 ofα4β2 nAChR antagonists towards neuropsychiatric dysfunctions.
文摘The authors regret that there was a picture error in Fig.5F owing to the inappropriate data statistics—forgetting gating when data collecting and a picture error in Fig.6F owing to the data copy mistake when drawing the column chart.The revisions cause some changes with the data value.
文摘The authors regret that there was a picture error in the Fig.6D1 owing to the image copy mistake of group-CORT when combining the images of different groups.The revision will cause no change with the data value in Fig.6D2,and also do not affect any conclusions of the current work and the description of the whole article.The authors have provided the original data of this figure to Editorial Office,and the corresponding authors or the Editorial Office can be contacted for original data access.
