Neuroprotective effects of Sijunzi Decoction on diabetes mellitus-associated cognitive impairment in mice
AIM To investigate the neuroprotective effects of Sijunzi Decoction on type 1 diabetes mellitus(DM)-associated cognitive impairment in mice.METHODS Four weeks after the intraperitoneal injection of STZ,the ICR mice with memory impairment confirmed by Morris water maze experiment were selected and randomly divided into the model group,the rapamycin group and the low-dose,medium-dose,and high-dose Sijunzi Decoction groups(1.56,3.12,and 6.24 g/kg).The mice had their levels of blood glucose and body mass detected;their glucose tolerance detected followed by 6 weeks corresponding administration,their serum insulin levels detected by ELISA;their learning and memory abilities assessed by Morris water maze experiment;their extinction of fear memory assessed by conditioned fear experiment;their histopathological changes in brain observed by HE staining and Nissl staining;their hippocampal SOD activity and MDA level detected by kits;and their hippocampal protein expressions of p-AMPK,p-mTOR,NR2A,NR2B,NR1,Shank 3 and PSD 95 detected by Western blot.RESULTS Intraperitoneal injection of STZ induced cognitive dysfunction in mice.Compared with the model group,the Sijunzi Decoction groups displayed reduced blood glucose,ameliorated cognitive dysfunction,attenuated hippocampal neuronal cell damage,inhibited hippocampal oxidative stress,upregulated p-AMPK,Shank 3,PSD 95,NR2A,NR2B,NR1 protein expressions,and downregulated p-mTOR protein expression.CONCLUSION Sijunzi Decoction can improve the insulin sensitivity,the neuronal cell damage,and thus the cognitive dysfunction in DM mice.And the mechanism may be related to the improvement of their synaptic protein expression,hippocampal synaptic homeostasis,and synaptic function through the AMPK/mTOR signaling pathway.