Microglia sense and suppress epileptic neuronal hyperexcitability

Yang Hu; Yuanyuan Yao; Honggang Qi; Jiurong Yang; Canyu Zhang; Aifeng Zhang; Xiufang Liu; Chenchen Zhang; Guangming Gan; Xinjian Zhu

Pharmacological Research (Sep 2023)

Microglia sense and suppress epileptic neuronal hyperexcitability

Yang Hu,
Yuanyuan Yao,
Honggang Qi,
Jiurong Yang,
Canyu Zhang,
Aifeng Zhang,
Xiufang Liu,
Chenchen Zhang,
Guangming Gan,
Xinjian Zhu

Affiliations

Yang Hu: Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Medical School of Southeast University, Nanjing, China
Yuanyuan Yao: Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Medical School of Southeast University, Nanjing, China
Honggang Qi: Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Medical School of Southeast University, Nanjing, China
Jiurong Yang: Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Medical School of Southeast University, Nanjing, China
Canyu Zhang: Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Medical School of Southeast University, Nanjing, China
Aifeng Zhang: Department of Pathology, Medical School of Southeast University, Nanjing, China
Xiufang Liu: Department of Pathogenic Biology and Immunology, Medical School of Southeast University, Nanjing, China
Chenchen Zhang: Transmission Electron Microscopy Center, Medical School of Southeast University, Nanjing, China
Guangming Gan: Transmission Electron Microscopy Center, Medical School of Southeast University, Nanjing, China; Department of Genetics and Developmental Biology, Medical School of Southeast University, Nanjing, China
Xinjian Zhu: Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Medical School of Southeast University, Nanjing, China; Correspondence to: Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Medical School of Southeast University, Dingjiaqiao 87th, Nanjing 210009, China.

Journal volume & issue: Vol. 195
p. 106881

Abstract

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Microglia are the resident immune cells of the central nervous system, undertaking surveillance role and reacting to brain homeostasis and neurological diseases. Recent studies indicate that microglia modulate epilepsy-induced neuronal activities, however, the mechanisms underlying microglia-neuron communication in epilepsy are still unclear. Here we report that epileptic neuronal hyperexcitability activates microglia and drives microglial ATP/ADP hydrolyzing ectoenzyme CD39 (encoded by Entpd1) expression via recruiting the cAMP responsive element binding protein (CREB)-regulated transcription coactivator-1 (CRTC1) from cytoplasm to the nucleus and binding to CREB. Activated microglia in turn suppress epileptic neuronal hyperexcitability in a CD39 dependent manner. Disrupting microglial CREB/CRTC1 signaling, however, decreases CD39 expression and diminishes the inhibitory effect of microglia on epileptic neuronal hyperexcitability. Overall, our findings reveal CD39-dependent control of epileptic neuronal hyperexcitability by microglia is through an excitation-transcription coupling mechanism.

Published in Pharmacological Research

ISSN: 1096-1186 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.sciencedirect.com/journal/pharmacological-research

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