1. Academic Validation
  2. Microglia sense and suppress epileptic neuronal hyperexcitability

Microglia sense and suppress epileptic neuronal hyperexcitability

  • Pharmacol Res. 2023 Aug 2;195:106881. doi: 10.1016/j.phrs.2023.106881.
Yang Hu 1 Yuanyuan Yao 1 Honggang Qi 1 Jiurong Yang 1 Canyu Zhang 1 Aifeng Zhang 2 Xiufang Liu 3 Chenchen Zhang 4 Guangming Gan 5 Xinjian Zhu 6
Affiliations

Affiliations

  • 1 Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Medical School of Southeast University, Nanjing, China.
  • 2 Department of Pathology, Medical School of Southeast University, Nanjing, China.
  • 3 Department of Pathogenic Biology and Immunology, Medical School of Southeast University, Nanjing, China.
  • 4 Transmission Electron Microscopy Center, Medical School of Southeast University, Nanjing, China.
  • 5 Transmission Electron Microscopy Center, Medical School of Southeast University, Nanjing, China; Department of Genetics and Developmental Biology, Medical School of Southeast University, Nanjing, China.
  • 6 Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Medical School of Southeast University, Nanjing, China. Electronic address: xinjianzhu@seu.edu.cn.
Abstract

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.

Keywords

AMP (PubChem CID: 6083); ATP (PubChem CID: 5957); Adenosine (PubChem CID: 60961); CD39; CREB; CRTC1; DPCPX (PubChem CID: 1329); Epilepsy; Microglia; Pilocarpine hydrochloride (PubChem CID: 5909).

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