Division of Neurology, Department of Internal Medicine, Saga University Faculty of Medicine, Saga, Japan.
J Alzheimers Dis. 2010;20(2):427-39. doi: 10.3233/JAD-2010-1381.
Innate immunity, especially that involving macrophage function, reportedly diminishes with advancing age and in patients with Alzheimer's disease (AD). In this study, we tried to elicit the non-specific activation of peripheral macrophages by oral administration of the herbal medicine Juzen-taiho-to (JTT), to assess its effect as a possible treatment for AD patients. Amyloid-beta protein precursor transgenic mice were used as a model of AD to clarify the effect of JTT. Activated macrophages derived from bone marrow cross the blood-brain barrier, and then develop into microglia, which phagocytose aggregated amyloid-beta (Abeta) in senile plaques. Here we show that orally administered JTT increased the number of CD11b-positive ramified microglia in the mouse brain. The immunohistochemical examination of brain sections stained with polyclonal anti-Abeta antibody showed reduced Abeta burden, and Abeta levels were also decreased in the insoluble fractions of brain homogenates, as determined by ELISA. Thus, the activation of peripheral macrophages by JTT might be a potential new therapeutic strategy for AD.
先天免疫，尤其是涉及巨噬细胞功能的先天免疫，据报道会随着年龄的增长而减弱，并且在阿尔茨海默病（AD）患者中也是如此。在这项研究中，我们试图通过口服草药方剂进行外周巨噬细胞的非特异性激活，以评估其作为 AD 患者潜在治疗方法的效果。使用淀粉样蛋白前体转基因小鼠作为 AD 模型来阐明 JTT 的作用。源自骨髓的活化巨噬细胞穿过血脑屏障，然后发育为小胶质细胞，后者吞噬老年斑中的聚集淀粉样蛋白（Abeta）。在这里，我们表明口服 JTT 增加了小鼠大脑中 CD11b 阳性树突状小胶质细胞的数量。用多克隆抗 Abeta 抗体染色的脑切片的免疫组织化学检查显示 Abeta 负荷减少，并且通过 ELISA 测定脑匀浆不溶性级分中的 Abeta 水平也降低。因此，JTT 对外周巨噬细胞的激活可能是 AD 的一种潜在新的治疗策略。
