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Investigation on the Expression of NMDA Receptor Subunit (NR1、NR2A、NR2B) in Different Brain Areas of Plumbum Exposure AD Rat Model

Author: ZhangQi
Tutor: ZhuQiWen
School: China Medical University
Course: Physiology
Keywords: Alzheimer’ s disease (AD) NR1 subunit NR2A subunit NR2B subunit
CLC: R749.16
Type: Master's thesis
Year: 2007
Downloads: 101
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Abstract


IntroductionThe N-methy-D-aspartate (NMDA) receptor is a subtype of the ionotropic Glutamatic acid receptor ,by investigating the pharmacology、physiology、pathbiology of NMDA receptor,we can confirm that the NMDA receptor have important physiological effect in development ,it can regulate neuronal activity、dendritic、axonal structural development and synaptic plasticity etc, in the form of neuronal circuit and the synaptic mechanism of learning and memory, NMDA receptor also play important role. Previous studies have suggested that glutamate-induced excitotoxic injury may disturb normal glutamate neurotransmission and glutamate receptor activation in a variety of neurological disorders including Alzheimer’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and epileptic disorders. It has also been reported that glutamate receptors can interact with amyloid precursor protein orβ-amyloid, which can lead to either beneficial or detrimental effects on neurons. These observations suggest that the NMDA receptor could play a significant role in the neurobiology of Alzheimer’s disease( AD).The establishment of AD animal model is the foundation of AD investigation. Review the investigation of AD, there are many dom and foreign laboratories , based on AD clinical feature and pathologic character, respectively develope various animal model in different angle, however, the animal model, including transgenic animal, cant stimulate or copy the primal pathological、biochemical、neurotransmitter and praxiology distinctive change absolute, restrict seriously the deeply study on AD pathogenesy and prevention. Accordingly, our study adopt Pb exposure to establish AD model rat, to study the change of NMDA receptor in AD model rat learning and memory disorder, approach the potential pathogenesy.Method1、Animal and establish modelThis experiment used 40 one month age Sprague-Dawley ( SD ), rats are grouped 5 without considering paroecious , normal control group have 8 rats ,fed with distilled water. Others are Pb exposure group, respectively fed with 0.1 %、0.2 %、0.5 %、1.0 % lead acetate prepared with distilled water. After 3 weeks diliver tomite, tomites weaning in from 21 days, fed with the same water and breed respectively.2、Passive avoidance response (PAR) train3、Use Western blot technique , determine the expression of NR1、NR2A and NR2B subunit protein in AD model rats brain cortex of frontal lobe、neocerebellum, hippocampus and corpora.4、Use RT-PCR technique, determine the expression of NR1、NR2A and NR2B subunit mRNA in AD model rats brain cortex of frontal lobe、neocerebellum、hippocampus and corpora.Results1、The levels of NR1、NR2A and NR2B subunit protein in different regions of the brain from AD model rats had different degree down regulate.2、The expression of NR1 subunit protein in the hippocampus of AD model rats had obviously reduce, the reduction in the cortex of frontal lobe and corpora striata was weak compared with hippocampus, there are no significant change in the neocerebellum.3、The expression of NR2A subunit protein had different reduction in the cortex of frontal lobe、neocerebellum、hippocampus and corpora striata of AD model rats, among the total, in the hippocampus had the most significant reduction, in the cortex of frontal lobe and corpora striata had significant reduction, the reduction in the neocerebellum was the weakest.4、The expression of NR2B subunit protein in different regions of the AD model rats had different degree reduction, among the total, the reduction in the hippocampus、 cortex of frontal lobe and corpora striata was significant, the neocerebellum had no obviously change.5、Among the expression of NR1、NR2A subunits mRNAs in the rat brains from normal controls, the neocerebellum was strong, others areas had no difference, NR2B subunit mRNA had strong expression in the cortex of frontal lobe and neocerebellum.6、The three subunits mRNAs expression in AD model rat group had different down regulation. NR1 subunit mRNA expression in the different regions form AD model rats were degrade, and the degree of down regulation had the same tendency; NR2A subunit mRNA expression had obviously reduction in the cortex of frontal lobe、neocerebellum、hippocampus and corpora striata from AD model rats; NR2B subunit mRNA expression had the most prominent reduction in the hippocampus, the reduction in the corpora striata was the better, in the neocerebellum had the weakest reduction .ConclusionThe expression of NMDA receptor subunits NR1、NR2A and NR2B protein and mRNA had different degree down regulation in the cortex of frontal lobe、neocerebellum、hippocampus and corpora striata from AD model rats.

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