• Login
    View Item 
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles
    • View Item
    •   UMB Digital Archive
    • UMB Open Access Articles
    • UMB Open Access Articles
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Traumatic Brain Injury Induces cGAS Activation and Type I Interferon Signaling in Aged Mice

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Author
    Barrett, James P
    Knoblach, Susan M
    Bhattacharya, Surajit
    Gordish-Dressman, Heather
    Stoica, Bogdan A
    Loane, David J
    Date
    2021-08-24
    Journal
    Frontiers in Immunology
    Publisher
    Frontiers Media S.A.
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.3389/fimmu.2021.710608
    Abstract
    Aging adversely affects inflammatory processes in the brain, which has important implications in the progression of neurodegenerative disease. Following traumatic brain injury (TBI), aged animals exhibit worsened neurological function and exacerbated microglial-associated neuroinflammation. Type I Interferons (IFN-I) contribute to the development of TBI neuropathology. Further, the Cyclic GMP-AMP Synthase (cGAS) and Stimulator of Interferon Genes (STING) pathway, a key inducer of IFN-I responses, has been implicated in neuroinflammatory activity in several age-related neurodegenerative diseases. Here, we set out to investigate the effects of TBI on cGAS/STING activation, IFN-I signaling and neuroinflammation in young and aged C57Bl/6 male mice. Using a controlled cortical impact model, we evaluated transcriptomic changes in the injured cortex at 24 hours post-injury, and confirmed activation of key neuroinflammatory pathways in biochemical studies. TBI induced changes were highly enriched for transcripts that were involved in inflammatory responses to stress and host defense. Deeper analysis revealed that TBI increased expression of IFN-I related genes (e.g. Ifnb1, Irf7, Ifi204, Isg15) and IFN-I signaling in the injured cortex of aged compared to young mice. There was also a significant age-related increase in the activation of the DNA-recognition pathway, cGAS, which is a key mechanism to propagate IFN-I responses. Finally, enhanced IFN-I signaling in the aged TBI brain was confirmed by increased phosphorylation of STAT1, an important IFN-I effector molecule. This age-related activation of cGAS and IFN-I signaling may prove to be a mechanistic link between microglial-associated neuroinflammation and neurodegeneration in the aged TBI brain. © Copyright © 2021 Barrett, Knoblach, Bhattacharya, Gordish-Dressman, Stoica and Loane.
    Rights/Terms
    Copyright © 2021 Barrett, Knoblach, Bhattacharya, Gordish-Dressman, Stoica and Loane.
    Keyword
    aging
    microglia
    neuroinflammation
    traumatic brain injury
    type I interferons
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/16649
    ae974a485f413a2113503eed53cd6c53
    10.3389/fimmu.2021.710608
    Scopus Count
    Collections
    UMB Open Access Articles

    entitlement

    Related articles

    • Interferon-β Plays a Detrimental Role in Experimental Traumatic Brain Injury by Enhancing Neuroinflammation That Drives Chronic Neurodegeneration.
    • Authors: Barrett JP, Henry RJ, Shirey KA, Doran SJ, Makarevich OD, Ritzel RM, Meadows VA, Vogel SN, Faden AI, Stoica BA, Loane DJ
    • Issue date: 2020 Mar 11
    • Activating cGAS-STING axis contributes to neuroinflammation in CVST mouse model and induces inflammasome activation and microglia pyroptosis.
    • Authors: Ding R, Li H, Liu Y, Ou W, Zhang X, Chai H, Huang X, Yang W, Wang Q
    • Issue date: 2022 Jun 10
    • cGAS knockdown promotes microglial M2 polarization to alleviate neuroinflammation by inhibiting cGAS-STING signaling pathway in cerebral ischemic stroke.
    • Authors: Jiang GL, Yang XL, Zhou HJ, Long J, Liu B, Zhang LM, Lu D
    • Issue date: 2021 Jun
    • STING-mediated type-I interferons contribute to the neuroinflammatory process and detrimental effects following traumatic brain injury.
    • Authors: Abdullah A, Zhang M, Frugier T, Bedoui S, Taylor JM, Crack PJ
    • Issue date: 2018 Nov 21
    • HDAC3 inhibition ameliorates ischemia/reperfusion-induced brain injury by regulating the microglial cGAS-STING pathway.
    • Authors: Liao Y, Cheng J, Kong X, Li S, Li X, Zhang M, Zhang H, Yang T, Dong Y, Li J, Xu Y, Yuan Z
    • Issue date: 2020
    DSpace software (copyright © 2002 - 2022)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.