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Complement factor C1q mediates sleep spindle loss and epileptic spikes after mild brain injury.
Holden, Stephanie S; Grandi, Fiorella C; Aboubakr, Oumaima; Higashikubo, Bryan; Cho, Frances S; Chang, Andrew H; Forero, Alejandro Osorio; Morningstar, Allison R; Mathur, Vidhu; Kuhn, Logan J; Suri, Poojan; Sankaranarayanan, Sethu; Andrews-Zwilling, Yaisa; Tenner, Andrea J; Luthi, Anita; Aronica, Eleonora; Corces, M Ryan; Yednock, Ted; Paz, Jeanne T.
Afiliação
  • Holden SS; Neurosciences Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Grandi FC; Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA.
  • Aboubakr O; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Higashikubo B; Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
  • Cho FS; Stichting Epilepsie Instellingen Nederland (SEIN), 2103 SW Heemstede, Netherlands.
  • Chang AH; Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA.
  • Forero AO; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Morningstar AR; Department of Fundamental Neurosciences, University of Lausanne, CH-1005 Lausanne, Switzerland.
  • Mathur V; Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
  • Kuhn LJ; Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA.
  • Suri P; Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
  • Sankaranarayanan S; Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA.
  • Andrews-Zwilling Y; Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
  • Tenner AJ; Neurosciences Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Luthi A; Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA.
  • Aronica E; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Corces MR; Department of Fundamental Neurosciences, University of Lausanne, CH-1005 Lausanne, Switzerland.
  • Yednock T; Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
  • Paz JT; Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, CA 94158, USA.
Science ; 373(6560): eabj2685, 2021 Sep 10.
Article em En | MEDLINE | ID: mdl-34516796
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtornos do Sono-Vigília / Fases do Sono / Tálamo / Lesões Encefálicas / Complemento C1q Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Science Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtornos do Sono-Vigília / Fases do Sono / Tálamo / Lesões Encefálicas / Complemento C1q Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Science Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos