Affiliations: [a]
Department of Biomedical Sciences, University of North Dakota School of Medicine & Health Sciences, Grand Forks, ND, USA
| [b] Veterinary Diagnostic Laboratory, North Dakota State University, Fargo, ND, USA
Correspondence:
[*]
Correspondence to: Colin K. Combs, 1301 North Columbia Road, Stop 9037, Department of Biomedical Sciences, University of North Dakota School of Medicine & Health Sciences, Grand Forks, ND 58202-9037, USA. Tel.: +1 701 777 4025; E-mail: [email protected].
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 AppNL-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 AppNL-G-F mice developed an IBD-like condition. Brain histologic and biochemical assessments demonstrated increased insoluble Aβ1–40/42 levels along with the decreased microglial CD68 immunoreactivity in DSS treated AppNL-G-F mice compared to vehicle treated AppNL-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.
