Intracerebroventricular administrations of angiotensin IV (Ang IV) ameliorate cognitive disorder in diabetic rats

Cognitive impairment is a common complication of diabetes. Hippocampus plays an important role in cognitive function. In hyperglycemia, synaptophysin, a crucial synaptic vesicle membrane protein in hippocampus neuron is found to be down-regulated. Recent evidences have shown that angiotensin IV can facilitate memory acquisition and recovery. However, whether it can also improve cognitive functions of diabetic rats with cognitive disorder, and the possible mechanisms are uncertain. Hence, the objectives of this study. Forty fi ve Sprague Dawley male rats were randomly divided into three groups: Control, diabetic group and diabetes with angiotensin IV treatment group. The cognitive functions, mainly learning and memory of the rats were evaluated using Morris water maze task. The synapses ultrastructure, relative mRNA concentrations and protein expression levels of synaptophysin in hippocampus CA1 area were estimated using transmission electron microscope, RT-PCR, immunohistochemistry and western blotting, respectively. Our study showed that in the diabetic rats with angiotensin IV treatment, the cognitive impairment as measured by Morris water maze task improved, the ultrastructure of synapses in hippocampus reversed, the relative mRNA concentrations and protein levels of synaptophysin in hippocampus signifi cantly increased, when compared with diabetic rats. We conclude that angiotensin IV plays an important role in improving cognitive function of diabetic rats. The possible mechanisms are up-regulating the expression of synaptophysin and normalizing the ultrastructure of synapses in hippocampus.