Diabetic Encephalopathy Affects Mitochondria and Axonal Transport Proteins

Introduction: Diabetic encephalopathy is described as any cognitive and memory impairments and associated with hippocampal degenerative changes, include neurodegenerative process and decreased number of living cell. Mitochondrial Diabetes (MD) appears fallowing activation of mutant mitochondrial DNA and is combination of diabetes and cognitive deficit. In this research we showed the correlation of diabetic encephalopathy, dysfunctional mitochondria and change in expression of axonal transport proteins (KIF5b, Dynein). Methods: Twenty four male Wistar rats were divided into three groups: (n=8):1_Control+saline 2_Diabetic, 3_Diabetic+Insulin. Before starting the experiments, animals with blood sugar lower than150mg/dl entered the study. Diabetes induction was carried out by STZ, IP administration. FBS and body weight was checked after 1week and at the end of the 8week. Then behavioral studies (elevated plus maze, Y-maze and passive avoidance learning) were performed. After behavioral studies, blood samples were taken to measure serum insulin level and HgbA1c. Then fresh hippocampal tissue was collected. Gene expression of motor proteins was assessed by R-T PCR and mitochondrial membrane potential was assessed by Rhodamine123. Results: Our results showed impairment of HgbA1c, serum insulin, FBS and weight in diabetic group (p<0.05).Behavioral tests, revealed different degrees of impairment in diabetic rats (p<0.05).KIF5b mRNA expression was increased in hippocampus (p<0.05) with no change in dynein gene expression. These changes were associated with abnormal mitochondrial membrane potential (p<0.05). Conclusion: KIF5b mRNA up-regulation in hippocampal neurons of STZ-diabetic rats is a factor which can be involved in abnormal axonal transport and decreased MMP, leading to impairment of mitochondrial function. These manifestations showed mitochondrial dysfunction on diabetes and resulted in abnormal behavioral tests and diabetic encephalopathy