The Effect Of DHA On Learning And Memory Of Diabetic Cognition Disorder Rats And Its Mechanism

Diabetes(diabetes mellitus,DM)is one of the most common chronic disease,causing central cognitive function damage,especially in the decline of learning and memory ability,which is closely related to Alzheimer's disease.The mechanisms of diabetic cognitive disorder is unknown,and there is not effective treatment and control method.Stromal cell derived factor 1(stromal cell-derived factor 1,SDF-1)is a kind of special chemotactic protein that affect the body's inflammatory reaction,chemokine receptor-4(chemokine receptor-4,CXCR4)is the specificity receptor of the SDF-1,which after the combination to participate in a variety of immune and inflammatory reaction of the body.Research reported that that plasma SDF-1 levels dropped in diabetic rats,the expression of CXCR4 in hippocampal CA1 pyramidal neurons was significantly lower.Docosahexaenoic acid(docosahexaenoic acid,DHA)is a series of n-3 polyunsaturated fatty acids(poly real-unsaturated fatty acids,PUFAs),higher levels was presented in brain tissue,clinical studies have shown that it is closely associated with neuronal plasticity and maintain cognitive function.ObjectiveTo study the effect of DHA on learning and memory in diabetic rats.To investigate the effect of DHA on the expression of SDF-1/CXCR4 in hippocampal neurons of diabetic rats.Methods40 healthy Sprague-Dawley rats were randomly divided into control into four groups:control group(Control),normal+DHA group(Control+DHA),diabetes(Diabetic)and diabetes+DHA(Diabetic+DHA)group,the latter two groups was fedwith high fat feed(20% lard based feed+80%).After 4 weeks fed with different diet,STZ(30 mg/kg)was injected to the rats in diabetes mellitus group and diabetes mellitus+DHA group.DHA was given daily in Control+DHA group and Diabetic+DHA group from the day of injection STZ.Body weight and blood glucose were tested regularly during the experiment.At the end of 10 weeks,after 10 th weeks,the rats were sacrificed,the level of TNF-?,SDF-1 were detected with ELISA methods and RT-PCR method.The expression of CXCR4 in rat hippocampal neurons was detected by immune-histochemistry.The phosphorylation of JNK was detected by Western Blotting method.Results1.Blood glucose and weight change: Two weeks after high-fat feeding,the weight of diabetes group and diabetes + DHA group was obviously higher than that of control group,72 h after the injection of STZ,blood glucose is significantly increased.Diabetes group and diabetes+DHA group rats showed a tendency to drink more,eat more,and pee more.DHA had no significant effect on blood glucose and weight in diabetic rats(P>0.05).2.The effect of DHA on space learning-memory ability in diabetic rats: In the spatial navigation experiment,the escape latency of diabetic group was significantly higher than that in the control group(P<0.05).In DHA intervention group,lower than that of the diabetic group.In search space experiment,The residence time in the target quadrant of the control group and the control DHA group was significantly higher than that of the other three quadrants.There was no significant difference in the percentage of the residence time in the four quadrants between the diabetic rats and the control group,and the retention time in the target quadrant was significantly reduced compared with the control group(P<0.05).DHA intervention significantly increased the residence time in the target quadrant although did not reach the level of control group(P<0.05).3.The effect of DHA on JNK phosphorylation levels in diabetic rat hippocampus:Compared with control group(P<0.05),the levels of JNK phosphorylation in hippocampal neurons of diabetic rats was increased,the phosphorylation of JNK of hippocampal neurons in diabetes+DHA group deareased.4.The effect of DHA on SDF-1 and TNF-? levels in the diabetic rats: The TNF-?protein and mRNA levels in diabetic rats were higher than those in the control group(P<0.05),and DHA significantly reduced TNF-? level.Moreover,The SDF-1 in the diabetic group was significantly lower than that in the control group,and DHA significantly increased the level SDF-1 in diabetic rats.5.The effect of DHA on the CXCR4 expression in hippocampal neurons of diabetic rats: Compared with the control group,the CXCR4 expression level decreased in diabetic rats.The intervention of DHA increased the number of CXCR4-positive neurons in hippocampus of diabetic rats(P<0.05).Conclusions1.There was no significant effect of DHA on blood glucose and weight in diabetic rats.2.DHA reduced the cognitive impairment of diabetic rats,and improved the learning and memory ability of diabetic rats.3.DHA inhibited TNF alpha and JNK phosphorylation in diabetic rats hippocampal neurons,decrease the level of inflammatory cytokines.4.DHA increased the level of SDF-1.5.DHA increased the number of CXCR4 positive neurons in hippocampus.