本文選題：慢性應(yīng)激 + 空間學(xué)習(xí)記憶　； 參考：《曲阜師范大學(xué)》2009年碩士論文

【摘要】： 許多研究顯示慢性應(yīng)激可損害健康,引發(fā)疾病,同時也可影響腦的認(rèn)知功能,導(dǎo)致學(xué)習(xí)記憶能力下降。腦源性神經(jīng)營養(yǎng)因子(BDNF)是神經(jīng)營養(yǎng)素家族的成員之一,它不僅對神經(jīng)元的生存、生長、分化有重要的影響,而且還能增強(qiáng)突觸聯(lián)系,影響神經(jīng)元的可塑性,并且與學(xué)習(xí)記憶有關(guān)。本研究采用多因素慢性(電擊足底、擁擠、擁擠+熱刺激,15天)應(yīng)激動物模型,研究了慢性應(yīng)激對不同月齡小鼠(2月齡和15月齡)空間學(xué)習(xí)記憶能力的損害作用及其BDNF在海馬和前腦皮層的表達(dá)變化。旨在探討慢性應(yīng)激對不同月齡小鼠空間學(xué)習(xí)記憶功能的影響及BDNF的作用,從而為指導(dǎo)臨床用藥提供一種新的措施和思路。 本研究以開場行為檢測小鼠在新異環(huán)境中的自發(fā)活動;采用Morris水迷宮測試小鼠空間學(xué)習(xí)記憶能力;通過HE染色觀察小鼠海馬和前腦皮層神經(jīng)細(xì)胞形態(tài)學(xué)的變化;采用免疫組織化學(xué)方法檢測BDNF在海馬和前腦皮層的表達(dá)。 研究結(jié)果如下: 1.與對照組小鼠相比,青年應(yīng)激組小鼠的爬行格數(shù)、直立次數(shù)及修飾次數(shù)均明顯減少,這一變化趨勢在老年應(yīng)激組小鼠更明顯,而糞便粒數(shù)沒有顯著性變化。與青年對照組小鼠相比,老年對照組小鼠的修飾次數(shù)顯著減少。與青年應(yīng)激組小鼠相比,老年應(yīng)激組小鼠爬行格數(shù)及修飾次數(shù)明顯減少。 2.應(yīng)激組小鼠尋找平臺的潛伏期較對照組小鼠明顯增加,且在空間搜索試驗(yàn)中,在目標(biāo)象限的停留時間較對照組小鼠明顯縮短,這種狀態(tài)持續(xù)到停止應(yīng)激后一周。分別與青年對照組和應(yīng)激組小鼠相比,老年對照組和應(yīng)激組小鼠的空間學(xué)習(xí)記憶能力略有降低,但是沒有統(tǒng)計(jì)學(xué)意義。 3.應(yīng)激組小鼠海馬神經(jīng)細(xì)胞的排列較對照組小鼠明顯疏松,細(xì)胞缺失,尼氏體淺染甚至溶解。前腦皮層神經(jīng)細(xì)胞也呈程度不同的損傷現(xiàn)象。與青年應(yīng)激組小鼠相比,老年應(yīng)激組小鼠的損傷更加嚴(yán)重。這種變化持續(xù)到停止應(yīng)激后一周。 4.應(yīng)激組小鼠海馬和前腦皮層BDNF表達(dá)均明顯下調(diào),陽性細(xì)胞數(shù)明顯減少,陽性細(xì)胞面積比顯著減小。老年應(yīng)激組小鼠變化尤為明顯。分別與青年對照組和應(yīng)激組小鼠相比,老年對照組和應(yīng)激組小鼠BDNF的表達(dá)顯著降低。 研究結(jié)論如下: 1.老年小鼠對新異環(huán)境的反應(yīng)性和耐受性均下降,慢性應(yīng)激后表現(xiàn)的更顯著,說明衰老是影響機(jī)體應(yīng)激反應(yīng)性的重要因素之一。 2.慢性應(yīng)激明顯損害小鼠的空間學(xué)習(xí)記憶能力,老年小鼠的空間學(xué)習(xí)記憶能力下降更明顯。 3.慢性應(yīng)激導(dǎo)致小鼠海馬和前腦皮層神經(jīng)細(xì)胞的形態(tài)學(xué)變化,老年組小鼠神經(jīng)細(xì)胞形態(tài)學(xué)改變較青年組小鼠加重。 4.慢性應(yīng)激可使小鼠海馬和前腦皮層BDNF的表達(dá)下降,老年組小鼠在海馬和前腦皮層BDNF的表達(dá)均較青年組小鼠下降明顯。 本研究發(fā)現(xiàn),慢性應(yīng)激后即刻及停止應(yīng)激后一周,小鼠的空間學(xué)習(xí)記憶功能的損傷與海馬和前腦皮層中BDNF表達(dá)的變化相一致,提示慢性應(yīng)激損害小鼠的空間學(xué)習(xí)記憶功能以及停止應(yīng)激后的恢復(fù)過程中,腦內(nèi)BDNF對其都發(fā)揮了重要的保護(hù)作用。
[Abstract]:Many studies have shown that chronic stress can damage health, cause disease, and also affect the cognitive function of the brain, resulting in a decline in learning and memory. BDNF is one of the members of the neurotrophic family, which not only affects the survival, growth, and differentiation of neurons, but also enhances synaptic connections. The plasticity of ringing neurons is related to learning and memory. In this study, the effects of chronic stress on the spatial learning and memory ability of different months of age (2 month old and 15 month old) and the changes in the expression of BDNF in the hippocampus and prefrontal cortex were studied by multiple factors chronic (electric shock, crowding, congestion + heat stimulation, 15 days). The purpose of this study is to explore the effect of chronic stress on the function of spatial learning and memory in mice of different months of age and the role of BDNF, so as to provide a new way to guide clinical medication.
In this study, the spontaneous activity of mice in the new environment was detected by the opening behavior; the Morris water maze was used to test the spatial learning and memory ability of mice; the morphological changes in the hippocampus and prefrontal cortex of mice were observed by HE staining, and the expression of BDNF in the hippocampus and prefrontal cortex was detected by immunohistochemistry.
The results of the study are as follows:
1. compared with the control group, the number of creeping, the erect times and the number of modification of the mice in the young stress group were significantly reduced, and the change trend was more obvious in the elderly stress group, but the number of fecal particles did not change significantly. Compared with the young control group, the number of modification times of the old control group decreased significantly. Compared with mice, the number of crawling lattices and the number of times of modification in the aged stress group decreased significantly.
In the 2. stress group, the incubation period of the finding platform was significantly higher than that of the control group. In the space search test, the stay time in the target quadrant was significantly shorter than the control group. This state lasted to the week after the stop stress. Compared with the young control group and the stress group, the spatial learning of the elderly control group and the stress group was compared with the stress group. The ability of learning and memory decreased slightly, but there was no statistical significance.
The hippocampal neurons in the 3. stress group were obviously looser than those in the control group, the cell loss, the Nissl body light staining and even dissolving. The nerve cells in the prefrontal cortex also showed a different degree of damage. Compared with the young stress group, the injury of the aged stress group was more serious. This change continued until the week after the stress was stopped.
In 4. stress group, the expression of BDNF in hippocampus and prefrontal cortex of mice was obviously decreased, the number of positive cells decreased and the ratio of positive cell area decreased significantly. The changes of mice in the elderly stress group were particularly obvious. Compared with the young control group and the stress group, the expression of BDNF in the elderly control group and the stress group decreased significantly.
The conclusions are as follows:
1. the reactivity and tolerance of the aged mice to the new environment decreased and the chronic stress was more significant, indicating that aging was one of the important factors affecting the stress responsiveness of the body.
2. chronic stress significantly impaired the spatial learning and memory ability of mice, and the spatial learning and memory ability of aged mice decreased more significantly.
3. chronic stress induced morphological changes of neurons in hippocampus and forebrain cortex of mice. The morphological changes of neurons in aged group were more serious than those in young mice.
4. chronic stress can reduce the expression of BDNF in the hippocampus and prefrontal cortex of mice. The expression of BDNF in the hippocampus and prefrontal cortex of the aged mice is significantly lower than that of the young mice.
This study found that the impairment of spatial learning and memory function in mice was consistent with the changes in the expression of BDNF in the hippocampus and prefrontal cortex after the immediate and halt stress after chronic stress. It suggested that the BDNF in the brain played an important role in the damage of the spatial learning and memory function of mice and the recovery process after the stress was stopped. Protection.
【學(xué)位授予單位】：曲阜師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2009
【分類號】：R363

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