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The Research on Ethology and Electrophysiology of Alzheimer’s Disease by the Modulation of PPARγ Agonist
Author: GuanQiao
Tutor: WangQinWen
School: Ningbo University
Course: Biochemistry and Molecular Biology
Keywords: PPARγ Rosiglitazone Morris water maze LTP inflammatory factor drug provided with potential value for AD treatment
CLC: R749.16
Type: Master's thesis
Year: 2011
Downloads: 44
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Abstract
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Objective:To investigate the roles of the PPARγagonist rosiglitazone on Alzheimer’s disease animal model ethology and LTP (long term potentiation ),so as to offer the new way and experimental foundation to illustrate the pathogenesis of AD(Alzheimer’s disease) and further offer the theoretical basis for the novel drugs development.Methods: 1.Ethology:Male and female wistar rats (270-300g) were used in experiment. The methods of the unilateral hippocampal drug injection implemented were used for the molding and drug therapy, the MWM (morris water maze) was employed for behavioral testing .2. Electrophysiology: Fresh tansverse slices of the hippocampus were prepared from male Wistar rats (age3–4weeks). Experimental drugs was administered by superfused ACSF(Artificial cerebrospinal fluid), the extracellular electrophysiological method was applied to record fEPSP(field excitatory postsynaptic potential) and LTP and EPSP peak value was taken as index, calculateing LTP amplitude. All values were normalized to percentage relative of foundation level. Recordings were analysed using p-CLAMP (Axon Instruments, CA, USA).All values are the means±SEM. and two-tailed Student’s t test and two-way ANOVA with repeated measures were used for measurement data comparison in experiment.Results:1. PPARγagonist rosiglitazone can improve the detriment of learning and memory of rats induced by Aβoligomer and in a dose-dependent manner. 2. rosiglitazone reverse the inhibition of LTP by Aβin time and concentration-dependent manner as well,in addition,showing the difference between acute function and chronic role. 3. Rosiglitazone can overturn the inhibition of proinflammatory cytokines IL-1β、IFNγon LTP. 4. PPARγspecific antagonist GW9662 can’t block the inhibition of LTP induction by Aβ、IL-1βand IFNγ.Conclusion:Rosiglitazone can ameliorate the ability of learning and memory of AD medol rats.As a kind of high-efficiency PPARγagonist, there are two different underling mechanisms by which rosiglitazone can improve the damage of LTP induction mediated by Aβand proinflammatory cytokines IL-1β、IFNγon LTP in a PPARγ-dependent manner and PPARγ-independent manner.These have suggested that PPARγagonist rosiglitazone may be a multi-target
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CLC: > Medicine, health > Neurology and psychiatry > Psychiatry > Cerebral organic mental disorder > Elderly as early as possible the old disorder
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