Gut Inflammation Induced by Dextran Sulfate Sodium Exacerbates Amyloid-β Plaque Deposition in the App NL–G–F Mouse Model of Alzheimer's Disease

M Sohrabi, HL Pecoraro… - Journal of Alzheimer's …, 2021 - content.iospress.com
M Sohrabi, HL Pecoraro, CK Combs
Journal of Alzheimer's Disease, 2021content.iospress.com
Background: Although it is known that the brain communicates with the gastrointestinal (GI)
tract via the well-established gut-brain axis, the influence exerted by chronic intestinal
inflammation on brain changes in Alzheimer's disease (AD) is not fully understood. We
hypothesized that increased gut inflammation would alter brain pathology of a mouse model
of AD. Objective: Determine whether colitis exacerbates AD-related brain changes. Methods:
To test this idea, 2% dextran sulfate sodium (DSS) was dissolved in the drinking water and …
Abstract
Background:
Although it is known that the brain communicates with the gastrointestinal (GI) tract via the well-established gut-brain axis, the influence exerted by chronic intestinal inflammation on brain changes in Alzheimer’s disease (AD) is not fully understood. We hypothesized that increased gut inflammation would alter brain pathology of a mouse model of AD.
Objective:
Determine whether colitis exacerbates AD-related brain changes.
Methods:
To test this idea, 2% dextran sulfate sodium (DSS) was dissolved in the drinking water and fed ad libitum to male C57BL/6 wild type and App NL-G-F mice at 6–10 months of age for two cycles of three days each. DSS is a negatively charged sulfated polysaccharide which results in bloody diarrhea and weight loss, changes similar to human inflammatory bowel disease (IBD).
Results:
Both wild type and App NL-G-F mice developed an IBD-like condition. Brain histologic and biochemical assessments demonstrated increased insoluble Aβ 1–40/42 levels along with the decreased microglial CD68 immunoreactivity in DSS treated App NL-G-F mice compared to vehicle treated App NL-G-F mice.
Conclusion:
These data demonstrate that intestinal dysfunction is capable of altering plaque deposition and glial immunoreactivity in the brain. This study increases our knowledge of the impact of peripheral inflammation on Aβ deposition via an IBD-like model system.
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