SAMP8小鼠海马突触活性带蛋白complexin及syntaxin1含量与年龄相关性空间学习记忆损害的关系
发布时间：2018-11-03 09:09
【摘要】：背景随着人口老年化进程的不断加快，老年相关疾病也受到人们的重视。脑老化是其中重要的研究课题。学习记忆能力下降是脑老化后认知功能衰退最早的表现之一。尽管已有不少研究，但衰老相关性记忆能力减退的机制仍不明确。现认为突触联络完整性的破坏是重要的原因之一。突触活性带蛋白complexin是突触前结构中重要的神经递质释放调节蛋白。其可逆地结合到SNAREs复合体上，调节复合体的四级结构，，从而调节递质的释放。Syntaxin1作为SNAREs复合体基本组成成分之一，特异地存在于突触前膜上。其与前膜蛋白SNAP25结合后，再与囊泡蛋白结合形成SNAREs三聚体，介导囊泡的搭靠和递质的释放。研究显示上述两种蛋白均与学习记忆密切相关。已发现complexin基因被敲除小鼠学习记忆能力显著下降。在经过记忆任务训练的老鼠，海马中syntaxin含量上升。然而，两者在正常衰老过程中的变化规律如何，是否与年龄相关性学习记忆损害有关尚缺少报告。 目的①探讨年龄对海马complexin1/2和syntaxin1含量的影响；②探讨海马complexin1/2和syntaxin1含量与空间性学习记忆能力年龄相关性损害间的关系。方法选取三个年龄段（4.5月、8月和13月）SAMP8小鼠，利用六臂辐射状水迷宫（RAWM）检测空间性学习记忆能力、免疫组织化学技术检测complexin1/2和syntaxin1含量在海马各亚区的表达（取平均光密度值作为蛋白的相对含量）。统计学分析涉及重复测定的方差分析、单因素方差分析、秩和检验和Spearman秩相关分析。 结果①13月龄小鼠在RAWM中的平均学习和记忆错误数／潜伏期均高于8月龄和4.5月龄组，8月龄组亦高于4.5月龄组。②与4.5月龄相比，13月龄组齿状回（DG）多形细胞层和外分子层及CA1区放射层的complexin1/2相对含量均显著下降。8月龄组后两者也下降。此外，13月龄组CA3透明层complexin1/2表达低于8月龄组。③与4.5月龄比，除DG门区和CA3透明层外，其余各层中13月龄组syntaxin1相对含量增加，8月龄组在DG分子层、CA1区分子层、放射层、起层及CA3锥体细胞层中相对含量增加。在DG颗粒细胞层、CA1锥体细胞层和起层中，13月龄组syntaxin1含量高于8月龄组。④CA1放射层complexin1/2含量与空间学习记忆能力正相关，CA1区、CA3区起层及DG区分子层的syntaxin1含量与空间学习记忆能力负相关。 结论SAMP8小鼠的空间学习记忆能力随年龄增加而下降，其海马DG区-CA3透明层-CA1放射层的complexin1/2含量呈环路特异的年龄相关性下降，而海马中syntaxin1含量在大部分层中呈年龄相关性增高。这些改变可能涉及年龄相关性空间学习记忆损害。
[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.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R749.1
本文编号：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.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R749.1
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