Effect Of Diabetes Mellitus On Cognition Of Vascular Dementia

Effect of diabetes mellitus on cognition of vascular dementiaVascular dementia (VaD) is an important cause of senile dementia, whose occurrence is secondary to that of Alzheimer's disease (AD). Clinically, VaD would make more sense in the prevention and treatment than AD does. Hence, more attention has been focused on VaD recently. Diabetes mellitus is also a common disease seriously banning human health. Epidemiological data showed that diabetes mellitus is one of the major risk factors of VaD, and the occurrence rate of dementia after stroke in diabetes patients is significantly higher than that of general healthy people. However, reports arc very few on the effect of diabetes mellitus on cognition, the central symptom of VaD. At the same time there are no ideal animal models of diabetes mellitus combined with VaD for research. We have established an animal model of chronic experimental diabetes mellitus combined with VaD to estimate the degree of brain damage in terms of histomorphology and cell apoptosis and to explore the effect of diabetes mellitus on the cognitive dysfunction induced by VaD. Cholinergic nervous system is closely related to study and memory. Studies showed that activity of ChAT, the marker enzyme of cholinergic system, is an important cause leading to dysfunction in study and memory. BDNF is one of the neurotrophic factors involved with the survival, differentiation and reparation of several classes of neurons. BDNF, rich in hippocampus, is involved with study and memory by modulating synaptic plasticity and inducing LTP. Moreover, to illuminate the relationship of diabetes mellitus and VaD, we observed the changes of ChAT protein and its mRNA level in CA1 area of hippocampus.PART I Effect of diabetes mellitus on cognition and morphology of VaD OBJECTIVE To establish an animal model of chronic experimental diabetes mellitus combined with VaD, and to observe the effect of diabetes mellitus on coanition andmorphology of VaD. METHODS Two-month-aged rats were trained to develop special study and memory with Y^maze. Rats reached to standards were injected slreplozotocin (STZ) into peritoneal cavity to induce experimental diabetes. One week later the bilateral common carotid arteries were permanently ligated to establish VaD models. The rats were randomly divided into four groups: (l)sham control group (2)sham diabetes mellitus group(DM) (3)VaD group (4)DM+VaD group. Record the weight and serum glucose and estimate the spacial study and memory in Y-maze. Then, (1 )HE stain and photograph, (2) Observe the activation of astrocyte by glia fibrillary acidic protein (GFAP) staining, (3)Apoptosis in CA1 area of hippocampus was measured with the use of a terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL) method. RESULTS (l)diabetic rats showed typical symptoms involving elevated serum glucose and weight loss (2)The rats in DM+VaD group reacted slower and made more error numbers in Y-maze than the rats in VaD group did, with a prolonged total reacting time in a whole day. (3)More neurons with serious damages, such as edema, ischemia or pyknosis could be found in DM+VaD group than in VaD group. More disarrangement of cone neurons, obvious glia proliferation, and more neuron apoptosis were found in CA] area of hippocampus. CONCLUSIONS (1)2-VO in STZ-induced diabetic rats succeeded in establishing VaD animal models. (2) The cognitive dysfunction induced by VaD rats had been deteriorated by diabetes mellitus. (3)Morphology evidences proved that diabetes mellitus aggravated brain damages induced by VaD.PART II Effect of diabetes mellitus on the cholinergic nervous systemin CA1 area of hippocampus of VaDOBJECTIVE To estimate the role of cholinergic nervous system in hippocampus during the process of cognitive dysfunction aggravated by diabetes mellitus in DM+VaD group. METHODS Observe the changes of ChAT protein by immunohistochemistry stain. Chose three rats randomly from each group at each pointat two week, four week, and eight week, then sepa...