记忆相关脑区中StAR与ChAT表达的相关性研究

发布时间：2018-05-19 02:04

本文选题：记忆 + 海马　；参考：《复旦大学》2010年硕士论文

【摘要】： 记忆是最重要的高级脑功能之一,脑内存在和记忆密切相关的特定结构,存在于这些记忆相关脑区中的胆碱能系统对记忆的形成与维持至关重要。衰老后记忆相关脑区中的胆碱能系统发生严重的退变,这种退变不仅表现在胆碱能神经元的形态上,更体现在其细胞功能上。然而衰老后记忆相关脑区中胆碱能系统发生退变的原因目前还没有定论。胆碱能系统功能的发挥由神经递质乙酰胆碱(Acetylcholine, Ach)介导,但由于Ach较易被胆碱酯酶降解,因此较为稳定的乙酰胆碱合成酶——胆碱乙酰转移酶(Choline acetyltransferase, ChAT)常被用来间接反应胆碱能系统功能状态。神经甾体是指能不依赖外周腺体而在神经系统中从头合成的甾体类化合物。甾体合成急性调节蛋白(Steroidogenic acute regulatory protein, StAR)介导着神经甾体合成的限速步骤,因此StAR可间接反映神经甾体的合成水平。脑内合成的神经甾体被证实具有重要的神经营养、神经保护及调节高级脑功能的作用。它们对胆碱能系统的作用也得到广泛的研究,神经甾体不仅可调节脑内胆碱能神经元的形态结构,更可调节对其细胞生物学功能。我们推测,衰老后记忆相关脑区内神经甾体合成的减少是存在于这些脑区中的胆碱能系统功能减退的重要原因。为此我们采用免疫荧光及Western blot方法,对1月龄、6月龄及24月龄雌性SD大鼠记忆相关脑区——海马、基底前脑及前额叶皮层中StAR及ChAT的表达情况进行检测,并对StAR与相应脑区中ChAT的表达量进行相关性分析。结果显示：在海马、基底前脑及前额叶皮层中均存在ChAT和StAR的表达；StAR可表达于上述脑区多种形态的细胞胞浆内；在所有脑区内,ChAT和StAR在24月龄组及1月龄组的表达量均显著低于对应的6月龄组(P0.05),而24月龄组略低于1月龄组(P0.05)；此外,StAR的表达量均与相应脑区中ChAT的表达量正相关。这些实验结果提示,记忆相关脑区存在神经甾体的合成,衰老后记忆相关脑区内神经甾体合成的减少是存在于该脑区中的胆碱能系统发生退变的重要原因之一。
[Abstract]:Memory is one of the most important advanced brain functions. The existence of specific structures in the brain is closely related to memory. The cholinergic system in these memory related brain regions is very important for the formation and maintenance of memory. The degeneration of cholinergic system in memory related brain after aging is not only reflected in the morphology of cholinergic neurons, but also in the cellular function of cholinergic neurons. However, the causes of degeneration of cholinergic system in memory-related brain area after aging are still unclear. The function of cholinergic system is mediated by acetylcholine (ache), but Ach is easily degraded by cholinesterase. Therefore, Choline acetyltransferase (ChAT), a stable acetylcholine synthase, is often used to indirectly reflect the functional state of cholinergic system. Neurosteroids are steroids that can be synthesized from scratch in the nervous system without relying on peripheral glands. Steroidogenic acute regulatory protein, StAR) mediates the rate-limiting step of neurosteroid synthesis, so StAR can indirectly reflect the level of neurosteroid synthesis. Neurosteroids synthesized in the brain have been proved to have important neurotrophic, neuroprotective and regulatory effects on advanced brain function. Their effects on cholinergic system have also been extensively studied. Neurosteroids can not only regulate the morphology of cholinergic neurons in the brain, but also regulate their cellular biological functions. We speculate that the decrease of neurosteroid synthesis in memory related brain regions after aging is an important reason for the decline of cholinergic system in these brain regions. For this purpose, the expression of StAR and ChAT in the memory related brain regions of 1-month and 24-month-old female Sprague-Dawley rats were detected by using immunofluorescence and Western blot methods, and the expression of StAR and ChAT in the basal forebrain and prefrontal cortex were detected. The correlation between StAR and the expression of ChAT in the corresponding brain region was analyzed. The results showed that ChAT and StAR were expressed in hippocampus, basal forebrain and prefrontal cortex. The expression of chat and StAR in all brain regions was significantly lower than that in the 6-month-old group (P0.05), while that in the 24-month-old group was slightly lower than that in the 1-month-old group, and the expression of star was positively correlated with the expression of ChAT in the corresponding brain region. These results suggest that the synthesis of neurosteroids exists in the memory related brain area, and the decrease of the neurosteroid synthesis in the memory related brain area after aging is one of the important reasons for the degeneration of cholinergic system in the memory related brain area.
【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R341

【共引文献】