Microglial TNF alpha; orchestrates protein phosphorylation in mouse cortical neurons 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 increased slow wave electroencephalograph activity that normally builds-up as the wake period increases and prevents immedi

SUBMITTER: Maria, Joana Pinto 

PROVIDER: S-SCDT-10_15252-EMBJ_2022111485 | biostudies-other |

REPOSITORIES: biostudies-other