中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (10): 2253-2259.doi: 10.4103/1673-5374.336875

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

射线损害海马CA1区锥体神经元的兴奋性放电及突触可塑性

  

  • 出版日期:2022-10-15 发布日期:2022-03-16
  • 基金资助:
    中国国家自然科学基金项目(81925031,81820108026,81972967,81872549)；中国自然科学基金青年项目(81801229)；广东省科技厅项目(2020B1212060018,2020B1212030004)；广东省自然科学基金项目(2019A1515011754)；广州市科技计划项目(202007030001)；广州市科技计划项目(201704030033)

Cranial irradiation impairs intrinsic excitability and synaptic plasticity of hippocampal CA1 pyramidal neurons with implications for cognitive function

Min-Yi Wu1, Wen-Jun Zou2, Pei Yu1, Yuhua Yang1, Shao-Jian Li1, Qiang Liu1, Jiatian Xie1, Si-Qi Chen3, Wei-Jye Lin4, 5, 6, Yamei Tang1, 4, 6   

  1. 1Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China; 2State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Key Laboratory of Psychiatric Disorders of Guangdong Province, Collaborative Innovation Center for Brain Science, Department of Neurobiology, Southern Medical University, Guangzhou, Guangdong Province, China; 3Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China; 4Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China; 5Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China; 6Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province, China
  • Online:2022-10-15 Published:2022-03-16
  • Contact: Wei-Jye Lin, PhD, linwj26@mail.sysu.edu.cn; Yamei Tang, MD, PhD, tangym@mail.sysu.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 81925031 (to YT), 81820108026 (to YT), 81972967 (to WJL), 81872549 (to YL); the Youth Program of National Natural Science Foundation of China, No. 81801229 (to YTX); a grant from Guangdong Science and Technology Department of China, Nos. 2020B1212060018 (to WJL), 2020B1212030004 (to WJL); the Natural Science Foundation of Guangdong Province, No. 2019A1515011754 (to WJL); the Science and Technology Program of Guangzhou of China, No. 202007030001 (to YT); and the Science and Technology Planning Project of Guangzhou of China, No. 201704030033 (to YL).

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摘要：

脑部放射治疗是头颈部肿瘤的标准治疗方法，但是接受放疗的患者常出现认知障碍。既往研究发现，海马功能障碍在射线引起的海马神经发生缺陷或神经炎症引起的认知障碍中起关键作用，但是射线对海马神经元电生理适应的长期影响尚知之甚少。因此实验对成年小鼠实施持续10min的强度为3Gy/min的单次辐射，3个月后可见小鼠出现认知障碍，且海马CA1区锥体神经元的尖峰放电以及锥体神经元兴奋性输入明显减少，而抑制性输入增加，对应的分子标记物VGLUT1表达降低而VGAT表达增加，同时损伤海马长时程增强并抑制GluR1表达。上述结果表明射线可损伤成熟海马神经元兴奋性放电及突触可塑性。

https://orcid.org/0000-0002-6353-6107 (Yamei Tang); https://orcid.org/0000-0002-8392-7121 (Min-Yi Wu)

关键词: 射线性认知障碍, 全细胞膜片钳记录, 内在兴奋性, 自发兴奋性突触后电流, 自发抑制性突触后电流, 突触可塑性, 长时程增强, γ-氨基丁酸介导的功能亢进, I型囊泡谷氨酸转运蛋白, 囊泡γ-氨基丁酸转运蛋白, 谷氨酸受体1

Abstract: Radiation therapy is a standard treatment for head and neck tumors. However, patients often exhibit cognitive impairments following radiation therapy. Previous studies have revealed that hippocampal dysfunction, specifically abnormal hippocampal neurogenesis or neuroinflammation, plays a key role in radiation-induced cognitive impairment. However, the long-term effects of radiation with respect to the electrophysiological adaptation of hippocampal neurons remain poorly characterized. We found that mice exhibited cognitive impairment 3 months after undergoing 10 minutes of cranial irradiation at a dose rate of 3 Gy/min. Furthermore, we observed a remarkable reduction in spike firing and excitatory synaptic input, as well as greatly enhanced inhibitory inputs, in hippocampal CA1 pyramidal neurons. Corresponding to the electrophysiological adaptation, we found reduced expression of synaptic plasticity marker VGLUT1 and increased expression of VGAT. Furthermore, in irradiated mice, long-term potentiation in the hippocampus was weakened and GluR1 expression was inhibited. These findings suggest that radiation can impair intrinsic excitability and synaptic plasticity in hippocampal CA1 pyramidal neurons.

Key words: GABA-mediated hyperfunction, GluR, intrinsic excitability, long-term potentiation, radiation-induced cognitive impairment, spontaneous excitatory postsynaptic currents, spontaneous inhibitory postsynaptic currents, synaptic plasticity, type I vesicular glutamate transporter, vesicular GABA transporter, whole-cell patch clamp recording