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 (on line): 1-9.

• •    下一篇

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

  

  • 出版日期:2022-01-01 发布日期:2021-11-09

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:2022-01-01 Published:2021-11-09
  • Contact: Wei-Jye Lin, linwj26@mail.sysu.edu.cn; Yamei Tang, tangym@mail.sysu.edu.cn.
  • Supported by:
    This work was supported by the National Key R&D Program of China (2017YFC1307500, 2017YFC1307504), the National Natural Science Foundation of China (81925031, 81820108026), and the Science and Technology Program of Guangzhou (202007030001) to Yamei Tang; Guangdong Science and Technology Department (2020B1212060018, 2020B1212030004), the National Natural Science Foundation of China (81972967), and the Natural Science Foundation of Guangdong Province (2019A1515011754) to Wei-Jye Lin; the Science and Technology Planning Project of Guangzhou (201704030033), and the National Natural Science Foundation of China (81872549) to Yi Li; the Youth Program of National Natural Science Foundation of China (81801229) to Yongteng Xu.

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

Abstract: Radiation therapy (RT) is a standard treatment for head and neck tumors. However, radiation-induced cognitive impairment remains a serious issue due to lack of satisfying prevention and effective treatment. Previous studies have revealed that dysfunction of the hippocampus played a key role in radiation-induced cognitive impairment resulted from hippocampal neurogenesis deficit or neuroinflammation. However, the long-term effect of radiation on electrophysiological adaptation of hippocampal neurons remains poorly recognized. This investigation focused on the impact of 30 Gy radiation-induced functional alternation in the hippocampal neurons by systematically assessing intrinsic physiology, synaptic plasticity and molecular markers in the mice at three months post irradiation. Our results demonstrated that radiation diminished the spike firing of hippocampal CA1 pyramidal neurons. In addition, radiation also reduced excitatory synaptic input and enhanced inhibitory inputs on CA1 pyramidal neurons, in accordance with decreased VGLUT1 and increased VGAT expression in the hippocampus, indicating radiation may have a direct impact on the excitatory/inhibitory balance of synaptic input in the hippocampus. Furthermore, we demonstrated the impaired hippocampal long-term potentiation (LTP) with marked alteration of the GluR1 expression levels at three months post irradiation. Since the radiation-induced hippocampal dysfunction is associated with spatial memory impairment, our findings provide new insights into the pathogenic mechanism underlying radiation-induced cognitive deficits.

Key words: radiation-induced cognitive impairment, whole-cell patch clamp recording, intrinsic excitability, spontaneous excitatory postsynaptic currents, spontaneous inhibitory postsynaptic currents, synaptic plasticity, long-term potentiation, GABA-mediated hyperfunction, type I vesicular glutamate transporter, vesicular GABA transporter, GluR1