Microglia sense and suppress epileptic neuronal hyperexcitability.

Humans Microglia Brain / metabolism Signal Transduction Epilepsy / metabolism
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)

Journal

Pharmacological research
ISSN: 1096-1186
Titre abrégé: Pharmacol Res
Pays: Netherlands
ID NLM: 8907422

Informations de publication

Date de publication:
09 2023
Historique:
received: 31 05 2023
revised: 15 07 2023
accepted: 01 08 2023
medline: 11 9 2023
pubmed: 5 8 2023
entrez: 4 8 2023
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.phrs.2023.106881 PMID: 37541638
pubmed: 37541638
pii: S1043-6618(23)00237-2
doi: 10.1016/j.phrs.2023.106881
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

106881

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Yang Hu (Y)

Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Medical School of Southeast University, Nanjing, China.

Yuanyuan Yao (Y)

Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Medical School of Southeast University, Nanjing, China.

Honggang Qi (H)

Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Medical School of Southeast University, Nanjing, China.

Jiurong Yang (J)

Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Medical School of Southeast University, Nanjing, China.

Canyu Zhang (C)

Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Medical School of Southeast University, Nanjing, China.

Aifeng Zhang (A)

Department of Pathology, Medical School of Southeast University, Nanjing, China.

Xiufang Liu (X)

Department of Pathogenic Biology and Immunology, Medical School of Southeast University, Nanjing, China.

Chenchen Zhang (C)

Transmission Electron Microscopy Center, Medical School of Southeast University, Nanjing, China.

Guangming Gan (G)

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 (X)

Department of Pharmacology, Jiangsu Provincial Key Laboratory of Critical Care Medicine, Medical School of Southeast University, Nanjing, China. Electronic address: xinjianzhu@seu.edu.cn.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Microglia sense and suppress epileptic...
questionsmedicales.fr › Cellules › Névroglie › Microglie › Microglia sense and suppress epileptic...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Microglia sense and suppress epileptic...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Microglia sense and suppress epileptic...
questionsmedicales.fr › Maladies du système nerveux › Maladies du système nerveux central › Encéphalopathies › Épilepsie › Microglia sense and suppress epileptic...