The Study Of CHOP, Caspase-12 Expression On The Hippocampus Of Diabetic Model Rat Induced By Streptozotocin

Diabetes mellitus (DM) may give rise to cognitive impairment, however the molecular mechanism involved was still unknown. We employed streptozotocin (STZ)-induced diabetic rats and tested their capacity for learning and memory by Morris water maze test. We also cultured hippocampal neurons in high glucose medium. The expression level of CHOP/GADD153 and Caspase-12 protein in the hippocampus neurons were examined by immunohistochemistry and Western Blot method. The ultrastructures of hippocampal neurons were observed by transmission electron microscopy (TEM) in vivo and by scanning electron microscopy (SEM) in vitro. Six weeks after STZ induction, the diabetic rats demonstrated decreased capacity for learning and memory as indicated by the increase in the escape latency and the decrease in the times of searching to the platform in Morris water maze test(P<0.01). TEM results illustrated the ultrastructures of diabetes hippocampus in the dentate gyrus (DG) neurons were characterized by apoptosis of swollen mitochondria, reduced synaptic contacts. The expression level of CHOP and Caspase-12 increased significantly in the hippocampal area in diabetic rats (P<0.01). After 24 h culturing in high glucose medium, we also determined that more neurons become apoptosis by SEM and the network constructed by neurons'neurites become incomplete and rare. The expression level of CHOP and Caspase-12 also increased significantly (P<0.01). These results indicated that DM could up-regulate CHOP and Caspase-12 expression in hippocampal area and then induce neurons'apoptosis in hippocampus, it may play a role in the pathogenesis of diabetic cognitive impairment.