Ameliorative Effects of Shi-Zhen-An-Shen Decoction on the Cognitive Impairment of MK801-Induced Rats: A Potential Therapeutic Approach for Schizophrenia

Cognitive dysfunction is a core feature of schizophrenia extremely correlates to the disabilities of community living and work of patients. It is evident that synaptic dysfunction results in similar cognitive and behavioral changes in rodents and/or humans that have been identified to occur in schizophrenia. Shi-Zhen-An-Shen decoction (SZASD) is a Chinese herbal medicine treating psychiatric symptoms, particularly cognitive impairment of schizophrenia patients at Beijing Anding Hospital. However, the mechanisms of SZASD on cognitive dysfunction of schizophrenia remain elusive. In this research, we aimed to investigate the underlying mechanisms of SZASD impacting on cognitive impairment of MK801-induced rats. Six groups (n =12 per group) of rats were subjected to different treatments for 14 days. Six groups were injected intraperitoneally with an equal volume of 0.9% saline and MK801 (0.2 mg/kg) for consecutive 14 days. And the rats in SZASD-treated groups and clozapine-treated group were administrated intragastrically with SZASD (low, middle, and high doses) or clozapine. Then, we performed behavioral tests after the treatments, and the rats were sacrificed on the 19 th day for biological analysis. We observed that SZASD could mitigate the aberrant motor activity, impaired spatial working memory, and the sensory gating dysfunction of rats in behavioral tests. Furthermore, our results showed that SZASD significantly improved the expressions of PSD95, BDNF, and synapsin I in hippocampus of MK801-treated rats. Our findings suggested that SZASD ameliorated the cognitive impairment potentially through restoring the levels of synaptic proteins in the hippocampus. We proposed that SZASD could be a potential therapeutic medicine to attenuate the cognitive impairment of schizophrenia for enhancing the synaptic proteins in the hippocampus.