| Objective To explore the effects of Ghrelin on the learning and memory abilities and the expressions of P-Tau and the WNT signaling pathways in the hippocampus of diabetic rats.Methods:60 male SD rats were randomly assigned into 4 groups, namely the control group(NC group), diabetic group( DM group),Ghrelin-treated diabetic group(DM1 group), Ghrelin and GHSR-1a receptor antagonist D-lys3-GHRP-6-treated diabetic group(DM2 group). Diabetic rat models were established by a single intraperitoneal injection of streptozotocin(65 mg/kg). The learning and memory abilities of the rats were assessed with Morris water maze(MWM) test. Hippocampal CA1 area of the ultrastructure of rats to observe by electron microscope.The expressions of DKK-1 in serum were examined by elisa.The expressions of DKK-1、 β-catenin、p-GSK3、Tau and p-Tau in the hippocampus were examined by Quantitative Real-Time PCR and Western blotting.Results:Compared with the control group, the diabetic rats exhibited significantly impaired learning and memory abilities(P<0.05) with higher expression of DKK-1and lower β-catenin expression in the hippocampus(P<0.05) and significant ultrastructure injuriesanddisordered arrangement of neurons with the nucleus pycnosisin rat hippocampal CA1 area. After treatment with Ghrelin,the learning and memory abilities of the diabetic rats was remarkable improved(P<0.05), reduced DKK-1 and increasedβ-catenin expression(P<0.05), and the injured ultrastructurein rat hippocampal CA1 area was recovered to normal in some degreed neurons are arranged neatly with clear cell layer. Such effects of Ghrelin effect was blocked by treatment With D-lys3-GHRP-6 of the diabetic rats.Conclusion: Ghrelin could alleviate the learning and memory dysfunction in diabetic rats possibly by down-regulating the expressions of DKK-1 and activation of WNT signaling pathways. |
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