本文主要研究内容
作者丁艳霞(2019)在《衰老相关的大鼠初级视皮层神经元的功能衰退及轴突始段可塑性研究》一文中研究指出:衰老会伴随很多视觉能力的明显减弱,包括对视觉信号的方位和运动方向辨别、运动速度和亮度对比度检测等能力的下降。诸多电生理研究报道显示,这些老年性视觉能力的下降主要由于视觉皮层神经元随着衰老出现兴奋性升高,导致其对刺激信号的检测功能出现退化。近些年的研究结果显示,衰老相关的视皮层神经元的功能衰退可能与皮层内抑制作用的下降,尤其是GABA能抑制作用减弱有关。然而,最近关于衰老过程中GABA能递质系统分子标志物表达的研究结果却存在分歧,且神经元的功能衰退是否伴随着GABA能抑制作用的改变也未得到完全证实。另一方面,最近的研究表明,神经元轴突始段(AIS)的结构在应对神经元活动变化时具有高度的可塑性,以维持神经元兴奋性的稳定。衰老导致视觉皮层神经元兴奋性升高,这是否同时会触发神经元AIS的结构出现可塑性变化尚不可知。为了回答以上问题,本研究以老年和青年大鼠为研究对象,结合在体单细胞电生理记录、免疫荧光双标记和蛋白免疫印迹技术开展了系统的研究。首先,比较了青年和老年大鼠初级视皮层(V1)神经元的自发反应及对不同方位和运动方向视觉刺激的诱发反应,以明确衰老对V1神经元反应特性和功能的影响;其次,检测并比较青年和老年大鼠V1中GABA能神经递质分子标志物的表达,以评价衰老对视皮层内GABA能抑制作用的影响;最后,比较两个年龄组大鼠V1神经元AIS的长度以及在动作电位(AP)启动中起关键作用的Na+通道Nav1.6在AIS上的分布,以评价老年性V1神经元功能改变伴随的神经元AIS的可塑性变化。我们的结果发现:(1)与青年大鼠相比,老年大鼠V1神经元的平均自发反应和对视觉刺激的诱发反应均显著增加,信-噪比显著下降,表明衰老导致大鼠V1神经元的兴奋性升高;另外,老年大鼠V1神经元对非最优方位和运动方向的视觉刺激反应的增加幅度高于对最优方位和运动方向的视觉刺激反应的增加幅度,导致其对不同方位和运动方向刺激反应的选择性显著降低,表明衰老引起大鼠V1神经元对不同视觉信号的检测功能减弱;(2)与青年大鼠相比,老年大鼠V1各层中GABA阳性神经元占皮层神经元总数的比例显著减少,同时老年大鼠V1中GABA合成关键酶GAD67的含量显著降低,表现为GAD67的免疫荧光强度明显减弱以及GAD67的蛋白表达量显著减少,尽管GABA合成酶GAD65的免疫荧光强度和蛋白表达量在两个年龄组之间无显著差异。此外,老年大鼠V1中GABAAR的一个重要亚单位α1的免疫荧光强度和蛋白表达量亦较青年大鼠的显著减少。这些结果表明,衰老导致视觉皮层GABA能抑制作用减弱;(3)伴随老年大鼠V1神经元的兴奋性增强,其II/III层和V层神经元AIS的平均长度显著缩短;V1区Nav1.6的蛋白表达量显著减少,沿着AIS分布的Nav1.6的平均免疫荧光强度明显降低,尤其是AIS近胞体段Nav1.6的免疫荧光强度出现特异性降低,表明具有Nav1.6分布的AIS比例显著缩短。据以上结果分析推测,衰老引起AIS上Nav1.6离子通道数目减少,这将会使V1神经元兴奋时Na+内流减少,兴奋恢复过程中Na+-K+泵消耗ATP减少,从而有利于弥补衰老过程中V1神经元放电频率增加而引起的能量过度消耗。综上所述,本研究发现衰老导致大鼠V1神经元的兴奋性显著增强,对视觉信号的检测功能下降,这种神经元功能衰退伴随视皮层内GABA能递质系统分子标志物表达的减少,该实验结果表明皮层内GABA能抑制性神经递质系统作用的减弱可能是引起皮层神经元功能减退的重要因素。另外,我们的研究亦提示,老化的视皮层神经元在出现兴奋性升高和功能退化的同时,也可通过AIS结构可塑性方式进行适应性代偿,以维持脑内能量收支的平衡。
Abstract
cui lao hui ban sui hen duo shi jiao neng li de ming xian jian ruo ,bao gua dui shi jiao xin hao de fang wei he yun dong fang xiang bian bie 、yun dong su du he liang du dui bi du jian ce deng neng li de xia jiang 。zhu duo dian sheng li yan jiu bao dao xian shi ,zhe xie lao nian xing shi jiao neng li de xia jiang zhu yao you yu shi jiao pi ceng shen jing yuan sui zhao cui lao chu xian xing fen xing sheng gao ,dao zhi ji dui ci ji xin hao de jian ce gong neng chu xian tui hua 。jin xie nian de yan jiu jie guo xian shi ,cui lao xiang guan de shi pi ceng shen jing yuan de gong neng cui tui ke neng yu pi ceng nei yi zhi zuo yong de xia jiang ,you ji shi GABAneng yi zhi zuo yong jian ruo you guan 。ran er ,zui jin guan yu cui lao guo cheng zhong GABAneng di zhi ji tong fen zi biao zhi wu biao da de yan jiu jie guo que cun zai fen qi ,ju shen jing yuan de gong neng cui tui shi fou ban sui zhao GABAneng yi zhi zuo yong de gai bian ye wei de dao wan quan zheng shi 。ling yi fang mian ,zui jin de yan jiu biao ming ,shen jing yuan zhou tu shi duan (AIS)de jie gou zai ying dui shen jing yuan huo dong bian hua shi ju you gao du de ke su xing ,yi wei chi shen jing yuan xing fen xing de wen ding 。cui lao dao zhi shi jiao pi ceng shen jing yuan xing fen xing sheng gao ,zhe shi fou tong shi hui chu fa shen jing yuan AISde jie gou chu xian ke su xing bian hua shang bu ke zhi 。wei le hui da yi shang wen ti ,ben yan jiu yi lao nian he qing nian da shu wei yan jiu dui xiang ,jie ge zai ti chan xi bao dian sheng li ji lu 、mian yi ying guang shuang biao ji he dan bai mian yi yin ji ji shu kai zhan le ji tong de yan jiu 。shou xian ,bi jiao le qing nian he lao nian da shu chu ji shi pi ceng (V1)shen jing yuan de zi fa fan ying ji dui bu tong fang wei he yun dong fang xiang shi jiao ci ji de you fa fan ying ,yi ming que cui lao dui V1shen jing yuan fan ying te xing he gong neng de ying xiang ;ji ci ,jian ce bing bi jiao qing nian he lao nian da shu V1zhong GABAneng shen jing di zhi fen zi biao zhi wu de biao da ,yi ping jia cui lao dui shi pi ceng nei GABAneng yi zhi zuo yong de ying xiang ;zui hou ,bi jiao liang ge nian ling zu da shu V1shen jing yuan AISde chang du yi ji zai dong zuo dian wei (AP)qi dong zhong qi guan jian zuo yong de Na+tong dao Nav1.6zai AISshang de fen bu ,yi ping jia lao nian xing V1shen jing yuan gong neng gai bian ban sui de shen jing yuan AISde ke su xing bian hua 。wo men de jie guo fa xian :(1)yu qing nian da shu xiang bi ,lao nian da shu V1shen jing yuan de ping jun zi fa fan ying he dui shi jiao ci ji de you fa fan ying jun xian zhe zeng jia ,xin -zao bi xian zhe xia jiang ,biao ming cui lao dao zhi da shu V1shen jing yuan de xing fen xing sheng gao ;ling wai ,lao nian da shu V1shen jing yuan dui fei zui you fang wei he yun dong fang xiang de shi jiao ci ji fan ying de zeng jia fu du gao yu dui zui you fang wei he yun dong fang xiang de shi jiao ci ji fan ying de zeng jia fu du ,dao zhi ji dui bu tong fang wei he yun dong fang xiang ci ji fan ying de shua ze xing xian zhe jiang di ,biao ming cui lao yin qi da shu V1shen jing yuan dui bu tong shi jiao xin hao de jian ce gong neng jian ruo ;(2)yu qing nian da shu xiang bi ,lao nian da shu V1ge ceng zhong GABAyang xing shen jing yuan zhan pi ceng shen jing yuan zong shu de bi li xian zhe jian shao ,tong shi lao nian da shu V1zhong GABAge cheng guan jian mei GAD67de han liang xian zhe jiang di ,biao xian wei GAD67de mian yi ying guang jiang du ming xian jian ruo yi ji GAD67de dan bai biao da liang xian zhe jian shao ,jin guan GABAge cheng mei GAD65de mian yi ying guang jiang du he dan bai biao da liang zai liang ge nian ling zu zhi jian mo xian zhe cha yi 。ci wai ,lao nian da shu V1zhong GABAARde yi ge chong yao ya chan wei α1de mian yi ying guang jiang du he dan bai biao da liang yi jiao qing nian da shu de xian zhe jian shao 。zhe xie jie guo biao ming ,cui lao dao zhi shi jiao pi ceng GABAneng yi zhi zuo yong jian ruo ;(3)ban sui lao nian da shu V1shen jing yuan de xing fen xing zeng jiang ,ji II/IIIceng he Vceng shen jing yuan AISde ping jun chang du xian zhe su duan ;V1ou Nav1.6de dan bai biao da liang xian zhe jian shao ,yan zhao AISfen bu de Nav1.6de ping jun mian yi ying guang jiang du ming xian jiang di ,you ji shi AISjin bao ti duan Nav1.6de mian yi ying guang jiang du chu xian te yi xing jiang di ,biao ming ju you Nav1.6fen bu de AISbi li xian zhe su duan 。ju yi shang jie guo fen xi tui ce ,cui lao yin qi AISshang Nav1.6li zi tong dao shu mu jian shao ,zhe jiang hui shi V1shen jing yuan xing fen shi Na+nei liu jian shao ,xing fen hui fu guo cheng zhong Na+-K+beng xiao hao ATPjian shao ,cong er you li yu mi bu cui lao guo cheng zhong V1shen jing yuan fang dian pin lv zeng jia er yin qi de neng liang guo du xiao hao 。zeng shang suo shu ,ben yan jiu fa xian cui lao dao zhi da shu V1shen jing yuan de xing fen xing xian zhe zeng jiang ,dui shi jiao xin hao de jian ce gong neng xia jiang ,zhe chong shen jing yuan gong neng cui tui ban sui shi pi ceng nei GABAneng di zhi ji tong fen zi biao zhi wu biao da de jian shao ,gai shi yan jie guo biao ming pi ceng nei GABAneng yi zhi xing shen jing di zhi ji tong zuo yong de jian ruo ke neng shi yin qi pi ceng shen jing yuan gong neng jian tui de chong yao yin su 。ling wai ,wo men de yan jiu yi di shi ,lao hua de shi pi ceng shen jing yuan zai chu xian xing fen xing sheng gao he gong neng tui hua de tong shi ,ye ke tong guo AISjie gou ke su xing fang shi jin hang kuo ying xing dai chang ,yi wei chi nao nei neng liang shou zhi de ping heng 。
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论文作者分别是来自安徽师范大学的丁艳霞,发表于刊物安徽师范大学2019-07-10论文,是一篇关于衰老论文,大鼠论文,初级视皮层论文,神经元功能衰退论文,合成酶论文,受体论文,轴突始段论文,电压门控性通道论文,安徽师范大学2019-07-10论文的文章。本文可供学术参考使用,各位学者可以免费参考阅读下载,文章观点不代表本站观点,资料来自安徽师范大学2019-07-10论文网站,若本站收录的文献无意侵犯了您的著作版权,请联系我们删除。
标签:衰老论文; 大鼠论文; 初级视皮层论文; 神经元功能衰退论文; 合成酶论文; 受体论文; 轴突始段论文; 电压门控性通道论文; 安徽师范大学2019-07-10论文;