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Complement C3 Aggravates Post-epileptic Neuronal Injury Via Activation of TRPV1

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Abstract

Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Recent studies have shown that complement component 3 (C3) aggravate the neuronal injury in epilepsy. And our previous studies revealed that TRPV1 (transient receptor potential vanilloid type 1) is involved in epilepsy. Whether complement C3 regulation of neuronal injury is related to the activation of TRPV1 during epilepsy is not fully understood. We found that in a mouse model of status epilepticus (SE), complement C3 derived from astrocytes was increased and aggravated neuronal injury, and that TRPV1-knockout rescued neurons from the injury induced by complement C3. Circular RNAs are abundant in the brain, and the reduction of circRad52 caused by complement C3 promoted the expression of TRPV1 and exacerbated neuronal injury. Mechanistically, disorders of neuron–glia interaction mediated by the C3–TRPV1 signaling pathway may be important for the induction of neuronal injury. This study provides support for the hypothesis that the C3–TRPV1 pathway is involved in the prevention and treatment of neuronal injury and cognitive disorders.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81571481 and 82060588), the Natural Science Foundation of Hubei Province, China (2017CFA017), the Wuhan Science and Technology Project (2019020701011444), and the Medical Science Advancement Program of Wuhan University (TFJC2018001 and TFLC2018001).

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Author notes

  1. Guang-Tong Jiang and Lin Shao contributed equally to this work.

Authors and Affiliations

  1. Department of Physiology, Hubei Provincial Key Laboratory of Developmentally Originated Disease, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China

    Guang-Tong Jiang, Lin Shao, Shuo Kong, Meng-Liu Zeng, Jing-Jing Cheng, Tao-Xiang Chen & Bi-Wen Peng

  2. Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China

    Song Han, Jun Yin & Xiao-Hua He

  3. Department of Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China

    Wan-Hong Liu

  4. Department of Neurology, Zhongnan Hospital, Wuhan University, Wuhan, 430071, China

    Yu-Min Liu

  5. Medical College, Tibet University, Lhasa, 850013, China

    Lanzi Gongga

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  1. Guang-Tong Jiang
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Correspondence to Bi-Wen Peng.

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Jiang, GT., Shao, L., Kong, S. et al. Complement C3 Aggravates Post-epileptic Neuronal Injury Via Activation of TRPV1. Neurosci. Bull. 37, 1427–1440 (2021). https://doi.org/10.1007/s12264-021-00750-4

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  • DOI: https://doi.org/10.1007/s12264-021-00750-4

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