本文選題：精神分裂癥 + 前額皮質(zhì)　； 參考：《寧夏醫(yī)科大學(xué)》2012年碩士論文

【摘要】：目的觀察小鼠在發(fā)生精神分裂癥癥狀后，刻板行為及共濟(jì)失調(diào)行為的變化情況，前額皮質(zhì)（PFC）和海馬（HIP）CA1、CA2、CA3內(nèi)GABA的變化情況。 方法應(yīng)用C57BL/6及GAD67-GFP基因敲入小鼠連續(xù)兩周腹腔注射不同劑量的地卓西平馬來酸鹽(MK801)（0.3mg/kg,0.6mg/kg,1mg/kg），進(jìn)行精神分裂癥動(dòng)物模型的制備。對注藥后3、5、7、10、14天小鼠的行為進(jìn)行錄像，對小鼠的共濟(jì)失調(diào)、刻板運(yùn)動(dòng)行為等進(jìn)行分析、評(píng)估；小鼠的精神分裂癥模型成功后，采用免疫熒光染色方法，觀察PFC和HIP的CA1、CA2、CA3內(nèi)GABA能神經(jīng)元以及GABA能神經(jīng)元亞群標(biāo)志物CB、CR、PV的變化；用RT-PCR方法，觀察上述腦區(qū)GAD67mRNA表達(dá)水平的改變。 結(jié)果（1）行為學(xué)改變�！�1刻板運(yùn)動(dòng)評(píng)估將0.3mg/kg、0.6mg/kg、1mg/kg三個(gè)劑量組小鼠的刻板運(yùn)動(dòng)評(píng)分進(jìn)行比較，結(jié)果顯示，0.6mg/kg、1mg/kg劑量組小鼠的刻板運(yùn)動(dòng)評(píng)分均較0.3mg/kg劑量組的顯著增高，分別增高37.9%、38.1%，而0.6mg/kg劑量組與1mg/kg劑量組之間評(píng)分無明顯差異；對給藥后第3、5、7、10、14天刻板運(yùn)動(dòng)進(jìn)行評(píng)分，隨著給藥天數(shù)的增加，各劑量組小鼠刻板運(yùn)動(dòng)評(píng)分均在逐漸減低。○2共濟(jì)失調(diào)評(píng)估將0.3mg/kg、0.6mg/kg、1mg/kg三個(gè)劑量組小鼠的共濟(jì)失調(diào)評(píng)分進(jìn)行比較，結(jié)果顯示，1mg/kg劑量組小鼠的刻板運(yùn)動(dòng)評(píng)分顯著高于0.3mg/kg劑量組的評(píng)分，增高36.4%，而0.3mg/kg劑量組與0.6mg/kg劑量組之間，1mg/kg劑量組與0.6mg/kg劑量組之間評(píng)分無明顯差異；對給藥后第3、5、7、10、14天共濟(jì)失調(diào)進(jìn)行評(píng)分，隨著給藥天數(shù)的增加，各劑量組小鼠共濟(jì)失調(diào)評(píng)分均在逐漸減低。（2）GABA能神經(jīng)元的變化。形態(tài)學(xué)方面�！�1PFC中，模型組和對照組小鼠各層均可見GFP陽性細(xì)胞，且在Ⅱ-Ⅲ層分布較多，但單位面積陽性細(xì)胞數(shù)與對照組無明顯差異；PV陽性細(xì)胞分布于Ⅲ-Ⅴ層，CB和CR陽性細(xì)胞主要分布于Ⅱ-Ⅲ層，但單位面積內(nèi)小清蛋白（PV）、鈣結(jié)合蛋白（CB）、鈣視網(wǎng)膜蛋白（CR）陽性細(xì)胞數(shù)目與對照組小鼠相比無明顯變化。○2HIP的CA1、CA2、CA3區(qū)，GFP陽性細(xì)胞在各層均有分布，但單位面積內(nèi)陽性細(xì)胞數(shù)與對照組相比無明顯變化；PV、CB陽性細(xì)胞主要分布于CA1的起始層，單位面積內(nèi)陽性細(xì)胞數(shù)與對照組無明顯差異；CR陽性細(xì)胞在CA1區(qū)較對照組明顯增多，，而在CA2及CA3區(qū)單位面積內(nèi)陽性細(xì)胞數(shù)較對照組無明顯差異。RT-PCR結(jié)果。精神分裂癥模型組小鼠，PFC中，GAD67mRNA的表達(dá)量較鹽水對照組明顯減少，而在海馬組織中，GAD67mRNA的表達(dá)量與鹽水對照組無明顯差異。 結(jié)論小鼠注射MK801后刻板運(yùn)動(dòng)及共濟(jì)失調(diào)行為具有劑量依賴性；長期給予1mg/kg及其以內(nèi)劑量的MK801可能使小鼠的刻板運(yùn)動(dòng)及共濟(jì)失調(diào)運(yùn)動(dòng)行為減弱，其可能與小鼠體內(nèi)遞質(zhì)的自我調(diào)節(jié)及小鼠的行為適應(yīng)有關(guān)；精神分裂癥時(shí)在PFC及HIP的CA1、CA2、CA3腦區(qū)抑制性神經(jīng)遞質(zhì)GABA在蛋白水平未見明顯改變；在mRNA水平上，GABA在PFC減少。這種變化與精神分裂癥的關(guān)系尚有待進(jìn)一步的研究。
[Abstract]:Objective to observe the changes of stereotypical behavior and ataxia behavior in mice after the onset of schizophrenia. Methods using C57BL / 6 and GAD67-GFP knockout mice for two consecutive weeks intraperitoneally injected different doses of didroxepine maleate (MK801) 0.3 mg / kg 0.6 mg / kg 路kg ~ (-1) mg 路kg ~ (-1) 路L ~ (-1) mg 路kg ~ (-1) ~ (-1) mg 路kg ~ (-1)? The behavior of mice was recorded on 3 days after injection, and the ataxia and stereotypical motor behavior of mice were analyzed and evaluated. After the success of the model of schizophrenia in mice, immunofluorescence staining was used. To observe the changes of GABA neurons and the subsets of GABA neurons in CA1, CA2 and CA3 of PFC and hip, and to observe the changes of CBB CRN PV, a subgroup marker of GABA neurons in PFC and hip. The changes of GAD67 mRNA expression in the above brain region were observed. Results 1) Behavioral changes. 01 stereotype motor evaluation. The stereotype motor scores of 0.3 mg / kg ~ 0.6 mg 路kg ~ (-1) 路kg ~ (-1) mg 路kg ~ (-1) were compared. The results showed that the scores of stereotype motor of mice in 0.6 mg / kg / kg group were significantly higher than those in 0.3mg/kg group, which were 37.9% and 38.1%, respectively, but there was no significant difference between the 0.6mg/kg group and the 1mg/kg group. With the increase of administration days, the stereotypical motor score of mice in each dose group was gradually decreased .02. The ataxia score of 0.3 mg / kg + 0.6 mg / kg + 1 mg / kg group was compared with that of the three dose groups. The results showed that the stereotype motor score of mice in the 1 mg / kg group was significantly higher than that in the 0.3mg/kg group and increased 36.4%, but there was no significant difference between the 1 mg / kg group and the 0.6mg/kg group in the 0.3mg/kg dose group and the 0.6mg/kg dose group. The ataxia scores of mice at day 3, 5, 7, 10 and 14 days after administration were evaluated. With the increase of administration days, the ataxia scores of mice in each dose group were gradually decreased. The changes of GABA neurons in each dose group were gradually decreased. In morphological aspect, GFP positive cells were found in each layer of model group and control group, and there were more GFP positive cells in layer 鈪

本文編號(hào)：1996935