| 蓝志达,王兆龙,谢先屿,赵乐文,方伟群.成年期视皮层神经元数量减少降低突触连接[J].,2024,(18):3401-3406 |
| 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 |
| 投稿时间：2024-02-06 修订日期：2024-02-28 |
| DOI：10.13241/j.cnki.pmb.2024.18.001 |
| 中文关键词: 视皮层 神经元 神经元数量 树突棘 |
| 英文关键词: Visual cortex Neuron Neuron number Dendritic spine |
| 基金项目:国家自然科学基金项目（32271023）；上海市浦江人才计划项目（22PJ1408900） |
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| 中文摘要: |
| 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。 |
| 英文摘要: |
| ABSTRACT 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. |
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