cGAS/STING and innate brain inflammation following acute high-fat feeding.

Autor:	Elzinga SE; Department of Neurology, University of Michigan, Ann Arbor, MI, United States.; NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI, United States., Henn R; Department of Neurology, University of Michigan, Ann Arbor, MI, United States.; NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI, United States., Murdock BJ; Department of Neurology, University of Michigan, Ann Arbor, MI, United States.; NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI, United States., Kim B; Department of Neurology, University of Michigan, Ann Arbor, MI, United States.; NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI, United States., Hayes JM; Department of Neurology, University of Michigan, Ann Arbor, MI, United States.; NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI, United States., Mendelson F; Department of Neurology, University of Michigan, Ann Arbor, MI, United States.; NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI, United States., Webber-Davis I; Department of Neurology, University of Michigan, Ann Arbor, MI, United States.; NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI, United States., Teener S; Department of Neurology, University of Michigan, Ann Arbor, MI, United States.; NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI, United States., Pacut C; Department of Neurology, University of Michigan, Ann Arbor, MI, United States.; NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI, United States., Lentz SI; Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, United States., Feldman EL; Department of Neurology, University of Michigan, Ann Arbor, MI, United States.; NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, MI, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Sep 29; Vol. 13, pp. 1012594. Date of Electronic Publication: 2022 Sep 29 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.1012594
Abstrakt:	Obesity, prediabetes, and diabetes are growing in prevalence worldwide. These metabolic disorders are associated with neurodegenerative diseases, particularly Alzheimer's disease and Alzheimer's disease related dementias. Innate inflammatory signaling plays a critical role in this association, potentially via the early activation of the cGAS/STING pathway. To determine acute systemic metabolic and inflammatory responses and corresponding changes in the brain, we used a high fat diet fed obese mouse model of prediabetes and cognitive impairment. We observed acute systemic changes in metabolic and inflammatory responses, with impaired glucose tolerance, insulin resistance, and alterations in peripheral immune cell populations. Central inflammatory changes included microglial activation in a pro-inflammatory environment with cGAS/STING activation. Blocking gap junctions in neuron-microglial co-cultures significantly decreased cGAS/STING activation. Collectively these studies suggest a role for early activation of the innate immune system both peripherally and centrally with potential inflammatory crosstalk between neurons and glia. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Elzinga, Henn, Murdock, Kim, Hayes, Mendelson, Webber-Davis, Teener, Pacut, Lentz and Feldman.)
Databáze:	MEDLINE
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