Department of Biomedical Sciences, University of North Dakota School of Medicine & Health Sciences, Grand Forks, ND, USA.
Veterinary Diagnostic Laboratory, North Dakota State University, Fargo, ND, USA.
J Alzheimers Dis. 2021;79(3):1235-1255. doi: 10.3233/JAD-201099.
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.
Determine whether colitis exacerbates AD-related brain changes.
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).
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.
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.
尽管已知大脑通过成熟的肠-脑轴与胃肠道（GI）进行通讯，但慢性肠道炎症对阿尔茨海默病（AD）中大脑变化的影响尚不完全清楚。我们假设肠道炎症的增加会改变 AD 小鼠模型的大脑病理学。
确定结肠炎是否会加剧 AD 相关的大脑变化。
为了验证这一想法，将 2%的葡聚糖硫酸钠（DSS）溶解在饮用水中，让 6-10 月龄的雄性 C57BL/6 野生型和 AppNL-G-F 小鼠自由饮用，每个周期持续三天，共两个周期。DSS 是一种带负电荷的硫酸化多糖，会导致血性腹泻和体重减轻，这些变化类似于人类炎症性肠病（IBD）。
野生型和 AppNL-G-F 小鼠均出现类似 IBD 的情况。大脑组织学和生物化学评估显示，与用载体处理的 AppNL-G-F 小鼠相比，DSS 处理的 AppNL-G-F 小鼠的可溶性 Aβ1-40/42 水平增加，小胶质细胞 CD68 免疫反应性降低。
这些数据表明，肠道功能障碍能够改变大脑中的斑块沉积和神经胶质免疫反应。这项研究通过类似 IBD 的模型系统增加了我们对周围炎症对 Aβ 沉积影响的认识。
