TY - JOUR
T1 - Complement factor C1q mediates sleep spindle loss and epileptic spikes after mild brain injury
AU - Holden, Stephanie S.
AU - Grandi, Fiorella C.
AU - Aboubakr, Oumaima
AU - Higashikubo, Bryan
AU - Cho, Frances S.
AU - Chang, Andrew H.
AU - Forero, Alejandro Osorio
AU - Morningstar, Allison R.
AU - Mathur, Vidhu
AU - Kuhn, Logan J.
AU - Suri, Poojan
AU - Sankaranarayanan, Sethu
AU - Andrews-Zwilling, Yaisa
AU - Tenner, Andrea J.
AU - Luthi, Anita
AU - Aronica, Eleonora
AU - Corces, M. Ryan
AU - Yednock, Ted
AU - Paz, Jeanne T.
N1 - Funding Information: This study was funded mainly by Department of Defense grant EP150038 to J.T.P., who also had support from the National Institutes of Health (NIH grant R01 NS078118), the National Science Foundation (NSF grant 1608236), Gladstone Institutes, the Michael Prize, the Vilcek Prize, and the Kavli Institute for Fundamental Neuroscience. S.S.H. was supported by an Achievement Rewards for College Scientists Scholarship, a Ford Foundation Dissertation Fellowship, the NIH (grant T32-GM007449), and the Weill Foundation. B.H. was supported by an American Epilepsy Society Postdoctoral Research Fellowship. F.S.C. was supported by the National Institute of Neurological Disorders and Stroke (NINDS grant F31 NS111819-01A1), the NSF (Graduate Research Fellowship 1144247), and by a UCSF Discovery Fellowship. E.A. was supported by Epilepsiefonds project 2020-02. A.L. was supported by the Swiss National Science Foundation (grant 310030-184759). A.O.F. was supported by the Faculty of Biology and Medicine?University of Lausanne doctoral fellowship. A.J.T. was supported by the NIH (grant R01AG060148). Publisher Copyright: © 2021 American Association for the Advancement of Science. All rights reserved.
PY - 2021/9/10
Y1 - 2021/9/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85114674090&partnerID=8YFLogxK
U2 - https://doi.org/10.1126/science.abj2685
DO - https://doi.org/10.1126/science.abj2685
M3 - Article
C2 - 34516796
SN - 0036-8075
VL - 373
JO - Science
JF - Science
IS - 6560
M1 - eabj2685
ER -