Applying vinpocetine to reverse synaptic ultrastructure by regulating BDNF-related PSD-95 in alleviating schizophrenia-like deficits in rat
Background: Schizophrenia is a mental disorder characterized by hyperlocomotion, cognitive symptoms, and social withdrawal. Brain-derived neurotrophic factor (BDNF) and postsynaptic density (PSD)-95 are related to schizophrenia-like deficits via regulating the synaptic ultrastructure, and play a rol...
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doaj-d4515c6e20e24407b57e038ceffb844c2020-11-25T01:39:51ZengElsevierComprehensive Psychiatry0010-440X2019-10-0194Applying vinpocetine to reverse synaptic ultrastructure by regulating BDNF-related PSD-95 in alleviating schizophrenia-like deficits in ratYue Xu0Chao Deng1Yongqiang Zheng2Nannuan Liu3Beibei Fu4Department of Neurology, Renmin Hospital, Hubei University of Medicine 39# Chaoyang Middle Road, Shiyan, Hubei 442000, PR ChinaDepartment of Neurology, Renmin Hospital, Hubei University of Medicine 39# Chaoyang Middle Road, Shiyan, Hubei 442000, PR ChinaDepartment of Neurology, The Second People's Hospital of Three Gorges University, 21# Xiling Yi Road, Yichang, Hubei 443002, PR ChinaDepartment of Neurology, Renmin Hospital, Hubei University of Medicine 39# Chaoyang Middle Road, Shiyan, Hubei 442000, PR ChinaDepartment of Neurology, Renmin Hospital, Hubei University of Medicine 39# Chaoyang Middle Road, Shiyan, Hubei 442000, PR China; Corresponding author.Background: Schizophrenia is a mental disorder characterized by hyperlocomotion, cognitive symptoms, and social withdrawal. Brain-derived neurotrophic factor (BDNF) and postsynaptic density (PSD)-95 are related to schizophrenia-like deficits via regulating the synaptic ultrastructure, and play a role in drug therapy. Vinpocetine is a nootropic phosphodiesterase-1 (PDE-1) inhibitor that can reverse ketamine-induced schizophrenia-like deficits by increasing BDNF expression. However, the effects of vinpocetine on alleviating schizophrenia-like deficits via reversing the synaptic ultrastructure by regulating BDNF-related PSD-95 have not been sufficiently studied. Methods: In this study, the schizophrenic model was built using ketamine (30 mg/kg) for 14 consecutive days. The effect of vinpocetine on reversing schizophrenia-like behaviors was examined via behavioral testing followed by treatment with certain doses of vinpocetine (20 mg/kg, i.p.). The BDNF and PSD-95 levels in the posterior cingulate cortex (PCC) were measured using biochemical assessments. In addition, the synaptic ultrastructure was observed using transmission electron microscopy (TEM). Results: Ketamine induced drastic schizophrenia-like behaviors, lower protein levels of BDNF and PSD-95, and a change in the synaptic ultrastructure in the PCC. After treatment, the vinpocetine revealed a marked amendment in schizophrenia-like behaviors induced by ketamine, including higher locomotor behavior, lower cognitive behavior, and social withdrawal defects. Vinpocetine could increase the PSD-95 protein level by up-regulating the expression of BDNF. In addition, the synaptic ultrastructure was changed after vinpocetine administration, including a reduction in the thickness and curvature of the synaptic interface, as well as an increase in synaptic cleft width in the PCC. Conclusion: Vinpocetine can reverse the synaptic ultrastructure by regulating BDNF-related PSD-95 to alleviate schizophrenia-like deficits induced by ketamine in rats. Keywords: Schizophrenia, Vinpocetine, BDNF, PSD-95, Synaptic ultrastructurehttp://www.sciencedirect.com/science/article/pii/S0010440X19300458 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yue Xu Chao Deng Yongqiang Zheng Nannuan Liu Beibei Fu |
spellingShingle |
Yue Xu Chao Deng Yongqiang Zheng Nannuan Liu Beibei Fu Applying vinpocetine to reverse synaptic ultrastructure by regulating BDNF-related PSD-95 in alleviating schizophrenia-like deficits in rat Comprehensive Psychiatry |
author_facet |
Yue Xu Chao Deng Yongqiang Zheng Nannuan Liu Beibei Fu |
author_sort |
Yue Xu |
title |
Applying vinpocetine to reverse synaptic ultrastructure by regulating BDNF-related PSD-95 in alleviating schizophrenia-like deficits in rat |
title_short |
Applying vinpocetine to reverse synaptic ultrastructure by regulating BDNF-related PSD-95 in alleviating schizophrenia-like deficits in rat |
title_full |
Applying vinpocetine to reverse synaptic ultrastructure by regulating BDNF-related PSD-95 in alleviating schizophrenia-like deficits in rat |
title_fullStr |
Applying vinpocetine to reverse synaptic ultrastructure by regulating BDNF-related PSD-95 in alleviating schizophrenia-like deficits in rat |
title_full_unstemmed |
Applying vinpocetine to reverse synaptic ultrastructure by regulating BDNF-related PSD-95 in alleviating schizophrenia-like deficits in rat |
title_sort |
applying vinpocetine to reverse synaptic ultrastructure by regulating bdnf-related psd-95 in alleviating schizophrenia-like deficits in rat |
publisher |
Elsevier |
series |
Comprehensive Psychiatry |
issn |
0010-440X |
publishDate |
2019-10-01 |
description |
Background: Schizophrenia is a mental disorder characterized by hyperlocomotion, cognitive symptoms, and social withdrawal. Brain-derived neurotrophic factor (BDNF) and postsynaptic density (PSD)-95 are related to schizophrenia-like deficits via regulating the synaptic ultrastructure, and play a role in drug therapy. Vinpocetine is a nootropic phosphodiesterase-1 (PDE-1) inhibitor that can reverse ketamine-induced schizophrenia-like deficits by increasing BDNF expression. However, the effects of vinpocetine on alleviating schizophrenia-like deficits via reversing the synaptic ultrastructure by regulating BDNF-related PSD-95 have not been sufficiently studied. Methods: In this study, the schizophrenic model was built using ketamine (30 mg/kg) for 14 consecutive days. The effect of vinpocetine on reversing schizophrenia-like behaviors was examined via behavioral testing followed by treatment with certain doses of vinpocetine (20 mg/kg, i.p.). The BDNF and PSD-95 levels in the posterior cingulate cortex (PCC) were measured using biochemical assessments. In addition, the synaptic ultrastructure was observed using transmission electron microscopy (TEM). Results: Ketamine induced drastic schizophrenia-like behaviors, lower protein levels of BDNF and PSD-95, and a change in the synaptic ultrastructure in the PCC. After treatment, the vinpocetine revealed a marked amendment in schizophrenia-like behaviors induced by ketamine, including higher locomotor behavior, lower cognitive behavior, and social withdrawal defects. Vinpocetine could increase the PSD-95 protein level by up-regulating the expression of BDNF. In addition, the synaptic ultrastructure was changed after vinpocetine administration, including a reduction in the thickness and curvature of the synaptic interface, as well as an increase in synaptic cleft width in the PCC. Conclusion: Vinpocetine can reverse the synaptic ultrastructure by regulating BDNF-related PSD-95 to alleviate schizophrenia-like deficits induced by ketamine in rats. Keywords: Schizophrenia, Vinpocetine, BDNF, PSD-95, Synaptic ultrastructure |
url |
http://www.sciencedirect.com/science/article/pii/S0010440X19300458 |
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