Complement factor C1q mediates sleep spindle loss and epileptic spikes after mild brain injury

Science. 2021 Sep 10;373(6560):eabj2685. doi: 10.1126/science.abj2685. Epub 2021 Sep 10.

Abstract

Although traumatic brain injury (TBI) acutely disrupts the cortex, most TBI-related disabilities reflect secondary injuries that accrue over time. The thalamus is a likely site of secondary damage because of its reciprocal connections with the cortex. Using a mouse model of mild TBI (mTBI), we found a chronic increase in C1q expression specifically in the corticothalamic system. Increased C1q expression colocalized with neuron loss and chronic inflammation and correlated with disruption in sleep spindles and emergence of epileptic activities. Blocking C1q counteracted these outcomes, suggesting that C1q is a disease modifier in mTBI. Single-nucleus RNA sequencing demonstrated that microglia are a source of thalamic C1q. The corticothalamic circuit could thus be a new target for treating TBI-related disabilities.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Brain Injuries / complications*
  • Brain Injuries / physiopathology
  • Complement C1q / genetics
  • Complement C1q / physiology*
  • Disease Models, Animal
  • Epilepsy / physiopathology
  • Mice
  • Microglia / metabolism
  • Sleep Stages*
  • Sleep Wake Disorders / etiology*
  • Sleep Wake Disorders / physiopathology*
  • Thalamus / metabolism
  • Thalamus / physiopathology*

Substances

  • C1qa protein, mouse
  • Complement C1q