Microglial TNFα orchestrates protein phosphorylation in the cortex during the sleep period and controls homeostatic sleep.

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

SUBMITTER: Pinto MJ 

PROVIDER: S-EPMC9811617 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature