Study On The Mechanism Of Cognitive Dysfun Ction Based On Hippocampal Camkii/Pka/Pkc Phosphorylation Signal Disorder In Diabetic Rats

As one of the chronic complications of diabetes, Diabetic cerebrovascular disease has attracted the attention of the clinical and basic researchers. However, the precise intracellular molecular mechanisms underlying diabetes-mediated deficits in learning and memory have not been fully elucidated.Objective:To investigate the alterations in hippocampal serine/threonine kinases signaling in the early phase of type1andtype2diabetic rats.Methods:Experimental diabetes mellitus was induced in rats with streptozotocin or streptozotocin/high fat. Changes in the phosphorylation of proteins were determined by immunoblotting and immunohistochemistry.Results:Our data showed a pronounced decrease in the phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the hippocampi of both type1and type2diabetic rats compared with age-matched control rats. Unexpectedly, we found a significant increase in the phosphorylation of Synapsin I (Ser603) and GluRl (Ser831) in the same experiment. In addition, aberrant changes in hippocampal protein kinase C (PKC) and protein kinase A (PKA) signaling in type1and type2diabetic rats were also found. Moreover, PP1α and PP2A protein levels were decreased in the hippocampus of type1diabetic rats, but significantly up-regulated in type2diabetic rats.Conclusions:The disturbance of CaMKⅡ/PKA/PKC phosphorylation in the hippocampus is an early change that may be associated with the development and progression of diabetes-related cognitive dysfunction.