Neural Regeneration Research ›› 2022, Vol. 17 ›› Issue (10): 2253-2259.doi: 10.4103/1673-5374.336875

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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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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