In:
Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-9-29)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2022.1012594
DOI:
10.3389/fimmu.2022.1012594.s001
DOI:
10.3389/fimmu.2022.1012594.s002
DOI:
10.3389/fimmu.2022.1012594.s003
DOI:
10.3389/fimmu.2022.1012594.s004
DOI:
10.3389/fimmu.2022.1012594.s005
DOI:
10.3389/fimmu.2022.1012594.s006
DOI:
10.3389/fimmu.2022.1012594.s007
DOI:
10.3389/fimmu.2022.1012594.s008
DOI:
10.3389/fimmu.2022.1012594.s009
DOI:
10.3389/fimmu.2022.1012594.s010
DOI:
10.3389/fimmu.2022.1012594.s011
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2606827-8
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