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 role in drug therapy. Vinpocetine is a nootropic phosphodiesterase-1 (PDE-1) inhibitor that can reverse ketamine-induced schizophrenia-like clefidts 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. (C) 2019 Published by Elsevier Inc.