SAMP8小鼠海馬突觸活性帶蛋白complexin及syntaxin1含量與年齡相關(guān)性空間學(xué)習(xí)記憶損害的關(guān)系
發(fā)布時(shí)間：2018-11-03 09:09
【摘要】：背景隨著人口老年化進(jìn)程的不斷加快，老年相關(guān)疾病也受到人們的重視。腦老化是其中重要的研究課題。學(xué)習(xí)記憶能力下降是腦老化后認(rèn)知功能衰退最早的表現(xiàn)之一。盡管已有不少研究，但衰老相關(guān)性記憶能力減退的機(jī)制仍不明確。現(xiàn)認(rèn)為突觸聯(lián)絡(luò)完整性的破壞是重要的原因之一。突觸活性帶蛋白complexin是突觸前結(jié)構(gòu)中重要的神經(jīng)遞質(zhì)釋放調(diào)節(jié)蛋白。其可逆地結(jié)合到SNAREs復(fù)合體上，調(diào)節(jié)復(fù)合體的四級(jí)結(jié)構(gòu)，，從而調(diào)節(jié)遞質(zhì)的釋放。Syntaxin1作為SNAREs復(fù)合體基本組成成分之一，特異地存在于突觸前膜上。其與前膜蛋白SNAP25結(jié)合后，再與囊泡蛋白結(jié)合形成SNAREs三聚體，介導(dǎo)囊泡的搭靠和遞質(zhì)的釋放。研究顯示上述兩種蛋白均與學(xué)習(xí)記憶密切相關(guān)。已發(fā)現(xiàn)complexin基因被敲除小鼠學(xué)習(xí)記憶能力顯著下降。在經(jīng)過記憶任務(wù)訓(xùn)練的老鼠，海馬中syntaxin含量上升。然而，兩者在正常衰老過程中的變化規(guī)律如何，是否與年齡相關(guān)性學(xué)習(xí)記憶損害有關(guān)尚缺少報(bào)告。 目的①探討年齡對(duì)海馬complexin1/2和syntaxin1含量的影響；②探討海馬complexin1/2和syntaxin1含量與空間性學(xué)習(xí)記憶能力年齡相關(guān)性損害間的關(guān)系。方法選取三個(gè)年齡段（4.5月、8月和13月）SAMP8小鼠，利用六臂輻射狀水迷宮（RAWM）檢測(cè)空間性學(xué)習(xí)記憶能力、免疫組織化學(xué)技術(shù)檢測(cè)complexin1/2和syntaxin1含量在海馬各亞區(qū)的表達(dá)（取平均光密度值作為蛋白的相對(duì)含量）。統(tǒng)計(jì)學(xué)分析涉及重復(fù)測(cè)定的方差分析、單因素方差分析、秩和檢驗(yàn)和Spearman秩相關(guān)分析。 結(jié)果①13月齡小鼠在RAWM中的平均學(xué)習(xí)和記憶錯(cuò)誤數(shù)／潛伏期均高于8月齡和4.5月齡組，8月齡組亦高于4.5月齡組。②與4.5月齡相比，13月齡組齒狀回（DG）多形細(xì)胞層和外分子層及CA1區(qū)放射層的complexin1/2相對(duì)含量均顯著下降。8月齡組后兩者也下降。此外，13月齡組CA3透明層complexin1/2表達(dá)低于8月齡組。③與4.5月齡比，除DG門區(qū)和CA3透明層外，其余各層中13月齡組syntaxin1相對(duì)含量增加，8月齡組在DG分子層、CA1區(qū)分子層、放射層、起層及CA3錐體細(xì)胞層中相對(duì)含量增加。在DG顆粒細(xì)胞層、CA1錐體細(xì)胞層和起層中，13月齡組syntaxin1含量高于8月齡組。④CA1放射層complexin1/2含量與空間學(xué)習(xí)記憶能力正相關(guān)，CA1區(qū)、CA3區(qū)起層及DG區(qū)分子層的syntaxin1含量與空間學(xué)習(xí)記憶能力負(fù)相關(guān)。 結(jié)論SAMP8小鼠的空間學(xué)習(xí)記憶能力隨年齡增加而下降，其海馬DG區(qū)-CA3透明層-CA1放射層的complexin1/2含量呈環(huán)路特異的年齡相關(guān)性下降，而海馬中syntaxin1含量在大部分層中呈年齡相關(guān)性增高。這些改變可能涉及年齡相關(guān)性空間學(xué)習(xí)記憶損害。
[Abstract]:Background with the rapid development of population aging, people pay more attention to geriatric diseases. Brain aging is one of the most important research topics. The decline of learning and memory is one of the earliest manifestations of cognitive decline after brain aging. Although a lot of research has been done, the mechanism of aging related memory decline is still unclear. It is believed that the destruction of synaptic connection integrity is one of the important reasons. Synaptic active band protein (complexin) is an important neurotransmitter release regulator in presynaptic structure. It reversibly binds to the SNAREs complex and regulates the quaternary structure of the complex, thereby regulating the release of transmitters. As one of the basic components of the SNAREs complex, Syntaxin1 specifically exists on the presynaptic membrane. It binds to promembrane protein SNAP25 and then binds to vesicle protein to form SNAREs trimer, which mediates vesicle attachment and release of transmitters. Studies have shown that both proteins are closely related to learning and memory. It was found that the ability of learning and memory of knockout mice with complexin gene decreased significantly. In mice trained with memory tasks, syntaxin levels increased in the hippocampus. However, there is no report on the relationship between the changes of the two during normal aging and the age-related impairment of learning and memory. Objective 1 to investigate the effect of age on the contents of complexin1/2 and syntaxin1 in hippocampus, and 2 to explore the relationship between complexin1/2 and syntaxin1 contents in hippocampus and the age-related impairment of spatial learning and memory ability. Methods the spatial learning and memory abilities of SAMP8 mice in three age groups (4.5, August and 13 months) were measured by using a six-arm radiative water maze (RAWM). Immunohistochemical technique was used to detect the expression of complexin1/2 and syntaxin1 in the hippocampal subareas (mean optical density as the relative content of protein). Statistical analysis involves repeated analysis of variance, single factor analysis of variance, rank sum test, and Spearman rank correlation analysis. Results the average number / latency of learning and memory errors in RAWM of 113-month-old mice was higher than that of 8-month-old and 4.5-month-old mice, and that of 8-month-old mice was also higher than that of 4.5-month-old mice. The relative contents of complexin1/2 in the (DG) polymorphic cell layer and the outer molecular layer and the radiation layer in the CA1 region of the odontoid gyrus decreased significantly in the 13-month-old group, as well as in the 8-month-old group. In addition, the expression of complexin1/2 in transparent layer of CA3 in 13-month-old group was lower than that in 8-month-old group. The relative content of syntaxin1 in 13-month-old group was higher than that in 8-month-old group, except DG portal area and CA3 transparent layer, and in the molecular layer of DG and CA1 region in 8-month-old group. The relative content of radiation layer, priming layer and CA3 pyramidal cell layer increased. In DG granulosa cell layer, CA1 pyramidal cell layer and initiation layer, the content of syntaxin1 in 13-month-old group was higher than that in 8-month-old group. The content of complexin1/2 in 4CA1 radiation layer was positively correlated with spatial learning and memory ability, and CA1 region. The content of syntaxin1 in the molecular layer of CA3 region and DG region was negatively correlated with spatial learning and memory ability. Conclusion the spatial learning and memory ability of SAMP8 mice decreases with age, and the content of complexin1/2 in the radiative layer of CA3 transparent layer-CA3 in hippocampal DG region is decreased in an age-specific manner. However, the content of syntaxin1 in hippocampus was increased in most layers. These changes may involve age-related spatial learning and memory impairment.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R749.1
本文編號(hào)：2307337
[Abstract]:Background with the rapid development of population aging, people pay more attention to geriatric diseases. Brain aging is one of the most important research topics. The decline of learning and memory is one of the earliest manifestations of cognitive decline after brain aging. Although a lot of research has been done, the mechanism of aging related memory decline is still unclear. It is believed that the destruction of synaptic connection integrity is one of the important reasons. Synaptic active band protein (complexin) is an important neurotransmitter release regulator in presynaptic structure. It reversibly binds to the SNAREs complex and regulates the quaternary structure of the complex, thereby regulating the release of transmitters. As one of the basic components of the SNAREs complex, Syntaxin1 specifically exists on the presynaptic membrane. It binds to promembrane protein SNAP25 and then binds to vesicle protein to form SNAREs trimer, which mediates vesicle attachment and release of transmitters. Studies have shown that both proteins are closely related to learning and memory. It was found that the ability of learning and memory of knockout mice with complexin gene decreased significantly. In mice trained with memory tasks, syntaxin levels increased in the hippocampus. However, there is no report on the relationship between the changes of the two during normal aging and the age-related impairment of learning and memory. Objective 1 to investigate the effect of age on the contents of complexin1/2 and syntaxin1 in hippocampus, and 2 to explore the relationship between complexin1/2 and syntaxin1 contents in hippocampus and the age-related impairment of spatial learning and memory ability. Methods the spatial learning and memory abilities of SAMP8 mice in three age groups (4.5, August and 13 months) were measured by using a six-arm radiative water maze (RAWM). Immunohistochemical technique was used to detect the expression of complexin1/2 and syntaxin1 in the hippocampal subareas (mean optical density as the relative content of protein). Statistical analysis involves repeated analysis of variance, single factor analysis of variance, rank sum test, and Spearman rank correlation analysis. Results the average number / latency of learning and memory errors in RAWM of 113-month-old mice was higher than that of 8-month-old and 4.5-month-old mice, and that of 8-month-old mice was also higher than that of 4.5-month-old mice. The relative contents of complexin1/2 in the (DG) polymorphic cell layer and the outer molecular layer and the radiation layer in the CA1 region of the odontoid gyrus decreased significantly in the 13-month-old group, as well as in the 8-month-old group. In addition, the expression of complexin1/2 in transparent layer of CA3 in 13-month-old group was lower than that in 8-month-old group. The relative content of syntaxin1 in 13-month-old group was higher than that in 8-month-old group, except DG portal area and CA3 transparent layer, and in the molecular layer of DG and CA1 region in 8-month-old group. The relative content of radiation layer, priming layer and CA3 pyramidal cell layer increased. In DG granulosa cell layer, CA1 pyramidal cell layer and initiation layer, the content of syntaxin1 in 13-month-old group was higher than that in 8-month-old group. The content of complexin1/2 in 4CA1 radiation layer was positively correlated with spatial learning and memory ability, and CA1 region. The content of syntaxin1 in the molecular layer of CA3 region and DG region was negatively correlated with spatial learning and memory ability. Conclusion the spatial learning and memory ability of SAMP8 mice decreases with age, and the content of complexin1/2 in the radiative layer of CA3 transparent layer-CA3 in hippocampal DG region is decreased in an age-specific manner. However, the content of syntaxin1 in hippocampus was increased in most layers. These changes may involve age-related spatial learning and memory impairment.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R749.1
【參考文獻(xiàn)】
相關(guān)期刊論文 前6條
1 楊啟綱;陳貴海;;年齡對(duì)SAMP8小鼠新物體再認(rèn)能力的影響[J];安徽農(nóng)業(yè)大學(xué)學(xué)報(bào);2006年02期
2 黃興圣;陳貴海;;昆明小鼠早期空間認(rèn)知功能損害具有任務(wù)特異性[J];安徽農(nóng)業(yè)大學(xué)學(xué)報(bào);2008年01期
3 左昕;潘奇波;林春輝;;學(xué)習(xí)記憶中長時(shí)記憶形成的分子機(jī)制[J];海軍醫(yī)學(xué)雜志;2008年04期
4 呂和平,任愛紅,武曉洛,王曉蘭,陳玲,李智濤;海馬在學(xué)習(xí)記憶中的作用研究進(jìn)展[J];洛陽醫(yī)專學(xué)報(bào);2002年04期
5 聶偉,張永祥;快速老化小鼠——研究衰老及衰老相關(guān)疾病的動(dòng)物模型[J];中國藥理學(xué)通報(bào);2000年02期
6 鄭君德;宋曉寧;蔡劍平;;淀粉樣前體蛋白在快速老化癡呆小鼠P8海馬中表達(dá)的免疫組化學(xué)研究[J];中日友好醫(yī)院學(xué)報(bào);2007年04期
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