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The Experimental Study Of Ecdysterone On Improvement Of The Learning And Memory In AD Animal Model

Posted on:2004-04-10Degree:DoctorType:Dissertation
Country:ChinaCandidate:S F YangFull Text:PDF
GTID:1104360092999766Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
By cell model in vitro and animal model in vivo, the effects of ECR on the learning and memory of AD animal and its protective mechanism were studied,in order to make a primary exploration in the AD therapy of ECR. The study included four parts: the toxicity to PC12 cells from H2O2 and A?25-35; AD model rats with dysfunction of learning and memory induced by microinjecting A?25-35 into the hippocampi; AD model mice with dysfunction of learning and memory induced by overload aluminium chloride microinjecting into the intracerebroventricle; the aggregation and the neurotoxicity of A?1-42 and the effects of ECR on them, especially on the oxidative and cholinergic system from the cerebral cortices. The results showed that, 50-100μM ECR could reduce the injury to PC12 cells from 100μM A?25-35 as well as 100μM H2O2, and the protective mechanism is probably that ECR could increase the activity of SOD and GSHpx and thus lowered the level of MDA; 8mg/kg ECR could still ameliorate the dysfuction oflearning and memory induced by A?25-35, which might involve in increas-ing the activities of SOD and ChAT, upregulating the expression of c-fos protein, and inhibiting the expression of NF-κB; However, 4mg/kg and 8mg/kg ECR failed to improve the dysfunction of learning and memory induced by the overload AlCl3, the reasons of which might be relative to too much overload of AlCl3 and the high level of AchE from the cerebral cortices; 100μM ECR could inhibit the aggregation, fibril-formation and the neurotoxicity of 100μM A?1-42 in vitro, which may result from inhibiting the expression of NF-κB. All above indicate that, ECR can improve the dysfunction of learning and memory induced by A?25-35, but whether ECR is used in the treatment of AD still needs further study and verification...
Keywords/Search Tags:Ecdysterone/ECR,AD,dysfunction of learning and memory,?-amyloid peptide,overload aluminium chloride,PC12 cells, neuron
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