成年期视皮层神经元数量减少降低突触连接  

Neuronal Loss in Adult Visual Cortex Reduces Synaptic Connection

作　　者：蓝志达 王兆龙[1] 谢先屿 赵乐文 方伟群 LAN Zhi-da;WANG Zhao-long;XIE Xian-yu;ZHAO Le-wen;FANG Wei-qun(Department of Anatomy and Physiology,Shanghai Jiao Tong University College of Basic Medical Sciences,Shanghai,200025,China)

机构地区：[1]上海交通大学基础医学院解剖学与生理学系,上海200025

出　　处：《现代生物医学进展》2024年第18期3401-3406,共6页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(32271023);上海市浦江人才计划项目(22PJ1408900)。

摘　　要：目的:探究成年期视皮层神经元数量减少对突触连接的改变,为解析创伤性脑损伤导致的视觉功能障碍提供实验依据。方法:采用立体定位技术,以腺相关病毒(Adeno-associated viruses,AAVs)稀疏感染方式于8周龄C57BL/6小鼠初级视皮层(Primary visual cortex,V1)中表达白喉毒素A片段蛋白(Diphtheria toxin A,DTA),引发神经元凋亡。4周后,通过免疫荧光染色、高尔基染色及共聚焦显微镜成像,分析视皮层第2-4层神经元数量以及幸存锥体神经元的树突棘形态特征。结果:通过注射不同滴度(E+11-13)的DTA表达病毒,成功构建了不同水平(14~85%)的视皮层神经元减少小鼠模型。结果发现低滴度(E+11)DTA表达病毒导致中等程度神经元减少(~18%,P<0.01),模拟了轻度创伤性脑损伤患者的皮层神经元丢失水平(16.5~22.9%),并发现该小鼠锥体神经元的树突棘密度与对照组没有差异,而树突棘成熟比例减少~19%(P<0.0001)。结论:成年期视皮层神经元数量减少损害突触连接,可能导致大脑的视觉功能障碍。Objective:Exploring the relationship between neuronal loss in adult visual cortex and its consequential changes in synaptic connection provides experimental evidence to elucidate impaired visual function upon traumatic brain injury.Methods:The primary visual cortex(V1)of 8-week-old C57BL/6 mice was sparsely infected with adeno-associated viruses(AAVs)encoding diphtheria toxin A(DTA)to induce neuronal apoptosis.Neuronal number and dendritic spine morphology of surviving pyramidal neurons in layers 2-4 of visual cortex were analyzed using immunofluorescence staining,Golgi staining and confocal microscopy after four weeks post-injection.Results:Through stereotactic injection of different titers(E+11-13)of DTA-expressing viruses,mouse models were generated with various levels of neuronal loss(by 14~85%)in the adult visual cortex.The results revealed that low-titer(E+11)DTA-expressing AAV led to moderate reduction of neuronal number(by~18%,P<0.01),mimicking the level of neuronal loss in patients with mild traumatic brain injury(16.5~2.9%).In this DTA group,while dendritic spine density of pyramidal neurons did not change in comparison to the control group,the proportion of mature spines reduced by~19%(P<0.0001).Conclusion:Neuronal loss in adult visual cortex impaired synaptic connection and probably compromised visual function in the brain.

关 键 词：视皮层 神经元 神经元数量 树突棘 

分 类 号：Q189[生物学—神经生物学] Q42[生物学—普通生物学]