Wu Min-Yi, Zou Wen-Jun, Yu Pei, Yang Yuhua, Li Shao-Jian, Liu Qiang, Xie Jiatian, Chen Si-Qi, Lin Wei-Jye, Tang Yamei
Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
State 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.
Neural Regen Res. 2022 Oct;17(10):2253-2259. doi: 10.4103/1673-5374.336875.
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.
放射治疗是头颈部肿瘤的标准治疗方法。然而，患者在放射治疗后常出现认知障碍。先前的研究表明，海马功能障碍，特别是异常的海马神经发生或神经炎症，在放射诱导的认知障碍中起关键作用。然而，关于海马神经元电生理适应性的放射长期影响仍知之甚少。我们发现，小鼠在以3 Gy/min的剂量率接受10分钟的颅脑照射3个月后出现认知障碍。此外，我们观察到海马CA1锥体神经元的放电和兴奋性突触输入显著减少，以及抑制性输入大大增强。与电生理适应性一致，我们发现突触可塑性标记物VGLUT1的表达减少，而VGAT的表达增加。此外，在受照射的小鼠中，海马中的长时程增强减弱，GluR1表达受到抑制。这些发现表明，放射可损害海马CA1锥体神经元的内在兴奋性和突触可塑性。
