The Relationship Between Ghrelin And Cognitive Dysfunction And The Intervention Of Telmisartan

Objective To observe the changes of Ghrelin and its receptor(GHSR1a) in hypothalamus, cerebral cortex and hippocampus in diabetic rats and investigate the possible protection mechanism of telmisartan on the cognitive function.Methods The male SD rats (weight 200±20 g) were randomly divided into three groups,namely the normal control group(N), diabetic model group(D) and the telmisartan treatment group(T). Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) at a dose of 60mg.kg-1in group D and group T. The telmisartan treatment group rats were treated with intragastric administration of telmisartan (13.3 mg.kg-1.day-1) from the onset of diabetes. After 12 weeks, all rats were tested in the Morris water maze, depressive disorder was excluded in Open-Field test. Ghrelin and GHSR1a in hypothalamus and cerebral cortex were detected by RT-PCR and immunohistochemical method respectively while only GHSR1a was determined in hippocampus by the two same methods respectively. Results In open-Field test, no significant differences were observed among groups (P>0.05).In Morris water maze, the escaping latency for group D was significantly prolonged than that for group N (P<0.05).Group T was shown to have a significantly decreased escape latencies than that for group D (P<0.05). Immunohistochemical showed that the protein expression of Ghrelin and GHSR1a of hypothalamus and cerebral cortex in group D was significantly lower than that in group N (P<0.05), with the protein expression of GHSR1a shown to be significantly lower in group D than in group N in hippocampus (P<0.05).Furthermore, group T was shown to have a significantly higher the protein expression of GHSR1a than in group D (P<0.05). RT-PCR were also declared that the level of mRNA of Ghrelin and GHSR1a in group D were all decreased significantly in hypothalamus and cerebral cortex than that in group N(P<0.05),while only GHSR1a was decreased significantly in hippocampus in group D than that in group N (P<0.05). Furthermore, group T was shown to have a significantly higher the level of mRNA of GHSR1a than in group D (P<0.05).Conclusion 1. The expression of Ghrelin and GHSR1a were down-regulated in diabetic rats.2. The cognition of group D was significantly decreased than group N.The cognitive impairement and the changes of GHSR1a in hippocampus of diabetic rats, suggested that these may related to diabetic cognitive disorder.3. Telmisartan early treatment can partially improve cognition, it may relate with its action on up-regulating GHSR1a of hippocampal.