Microglial TNFα orchestrates protein phosphorylation in the cortex during the sleep period and controls homeostatic sleep.
EMBO J
; 42(1): e111485, 2023 01 04.
Article
en En
| MEDLINE
| ID: mdl-36385434
ABSTRACT
Sleep intensity is adjusted by the length of previous awake time, and under tight homeostatic control by protein phosphorylation. Here, we establish microglia as a new cellular component of the sleep homeostasis circuit. Using quantitative phosphoproteomics of the mouse frontal cortex, we demonstrate that microglia-specific deletion of TNFα perturbs thousands of phosphorylation sites during the sleep period. Substrates of microglial TNFα comprise sleep-related kinases such as MAPKs and MARKs, and numerous synaptic proteins, including a subset whose phosphorylation status encodes sleep need and determines sleep duration. As a result, microglial TNFα loss attenuates the build-up of sleep need, as measured by electroencephalogram slow-wave activity and prevents immediate compensation for loss of sleep. Our data suggest that microglia control sleep homeostasis by releasing TNFα which acts on neuronal circuitry through dynamic control of phosphorylation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Factor de Necrosis Tumoral alfa
/
Microglía
Límite:
Animals
Idioma:
En
Revista:
EMBO J
Año:
2023
Tipo del documento:
Article
País de afiliación:
Francia