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The meningeal transcriptional response to traumatic brain injury and aging.
Bolte, Ashley C; Shapiro, Daniel A; Dutta, Arun B; Ma, Wei Feng; Bruch, Katherine R; Kovacs, Michael A; Royo Marco, Ana; Ennerfelt, Hannah E; Lukens, John R.
Afiliación
  • Bolte AC; Department of Neuroscience, Center for Brain Immunology and Glia (BIG), University of Virginia School of Medicine, Charlottesville, United States.
  • Shapiro DA; Department of Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, United States.
  • Dutta AB; Medical Scientist Training Program, University of Virginia School of Medicine, Charlottesville, United States.
  • Ma WF; Immunology Training Program, University of Virginia School of Medicine, Charlottesville, United States.
  • Bruch KR; Department of Neuroscience, Center for Brain Immunology and Glia (BIG), University of Virginia School of Medicine, Charlottesville, United States.
  • Kovacs MA; Medical Scientist Training Program, University of Virginia School of Medicine, Charlottesville, United States.
  • Royo Marco A; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, United States.
  • Ennerfelt HE; Medical Scientist Training Program, University of Virginia School of Medicine, Charlottesville, United States.
  • Lukens JR; Center for Public Health Genomics, University of Virginia School of Medicine, Charlottesville, United States.
Elife ; 122023 01 03.
Article en En | MEDLINE | ID: mdl-36594818
ABSTRACT
Emerging evidence suggests that the meningeal compartment plays instrumental roles in various neurological disorders, however, we still lack fundamental knowledge about meningeal biology. Here, we utilized high-throughput RNA sequencing (RNA-seq) techniques to investigate the transcriptional response of the meninges to traumatic brain injury (TBI) and aging in the sub-acute and chronic time frames. Using single-cell RNA sequencing (scRNA-seq), we first explored how mild TBI affects the cellular and transcriptional landscape in the meninges in young mice at one-week post-injury. Then, using bulk RNA-seq, we assessed the differential long-term outcomes between young and aged mice following TBI. In our scRNA-seq studies, we highlight injury-related changes in differential gene expression seen in major meningeal cell populations including macrophages, fibroblasts, and adaptive immune cells. We found that TBI leads to an upregulation of type I interferon (IFN) signature genes in macrophages and a controlled upregulation of inflammatory-related genes in the fibroblast and adaptive immune cell populations. For reasons that remain poorly understood, even mild injuries in the elderly can lead to cognitive decline and devastating neuropathology. To better understand the differential outcomes between the young and the elderly following brain injury, we performed bulk RNA-seq on young and aged meninges 1.5 months after TBI. Notably, we found that aging alone induced upregulation of meningeal genes involved in antibody production by B cells and type I IFN signaling. Following injury, the meningeal transcriptome had largely returned to its pre-injury signature in young mice. In stark contrast, aged TBI mice still exhibited upregulation of immune-related genes and downregulation of genes involved in extracellular matrix remodeling. Overall, these findings illustrate the dynamic transcriptional response of the meninges to mild head trauma in youth and aging.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Conmoción Encefálica / Lesiones Encefálicas / Lesiones Traumáticas del Encéfalo Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Elife Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Conmoción Encefálica / Lesiones Encefálicas / Lesiones Traumáticas del Encéfalo Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Elife Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
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