Juzen-Taiho-to, an herbal medicine, promotes the differentiation of transplanted bone marrow cells into microglia in the mouse brain injected with fibrillar amyloid β.

Abstract

Microglia are the main immunocompetent and phagocytic cells in Alzheimer's disease (AD). Bone marrow-derived microglia have been demonstrated to be more effective in antigen presentation and phagocytosis than inherent microglia in AD. Thus, microglia have received much attention in the pathogenesis of AD. The herbal medicine Juzen-taiho-to (JTT) has been reported to reduce β-amyloid (Aβ) burden in the mouse brain of an AD model. In this study, we explored the effects of JTT on the migration and differentiation of bone marrow-derived cells in the mouse brain of acutely induced AD. To chase bone marrow-derived cells, we made a chimeric mouse line in C57BL/6 by transplanting fresh bone marrow cells, isolated from the transgenic mice expressing enhanced green fluorescent protein gene. The chimeric mice were orally administrated with JTT or distilled water, and were left untreated or given intrahippocampal injection of fibrillar Aβ 1-42 (fAβ42) or vehicle. In the hippocampus of the vehicle-injected mouse, JTT treatment for 37 days caused a significant increase in the number of microglial cells. In the fAβ42-injected mouse hippocampus, a larger number of bone marrow-derived cells were detected in JTT-treated mice than control mice in the non-neighboring regions of the fAβ42-injected site but not around the injected site. These results suggest that JTT might contribute to the reduction of Aβ burden and the immune surveillance in non-pathological as well as pathological brain regions. The results also implicate the therapeutic potential of JTT in AD.