Metallothionein synthesis increased by Ninjin-yoei-to, a Kampo medicine protects neuronal death and memory loss after exposure to amyloid β(1-42)

BACKGROUND: It is possible that increased synthesis of metallothioneins (MTs), Zn(2+)-binding proteins is linked with the protective effect of Ninjin-yoei-to (NYT) on Zn(2+) toxicity ferried by amyloid β(1-42) (Aβ(1-42)). METHODS: Judging from the biological half-life (18-20 h) of MTs, the effective period of newly synthesized MT on capturing Zn(2+) is estimated to be approximately 2 days. In the present paper, a diet containing 3% NYT was administered to mice for 2 days and then Aβ(1-42) was injected into the lateral ventricle of mice. RESULTS: MT level in the dentate granule cell layer was elevated 2 days after administration of NYT diet, while the administration reduced intracellular Zn(2+) level increased 1 h after Aβ(1-42) injection, resulting in rescuing neuronal death in the dentate granule cell layer, which was observed 14 days after Aβ(1-42) injection. Furthermore, Pre-administration of NYT diet rescued object recognition memory loss via affected perforant pathway long-term potentiation after local injection of Aβ(1-42) into the dentate granule cell layer of rats. CONCLUSION: The present study indicates that pre-administration of NYT diet for 2 days increases synthesis of MTs, which reduces intracellular Zn(2+) toxicity ferried by extracellular Aβ(1-42), resulting in protecting neuronal death in the dentate gyrus and memory loss after exposure to Aβ(1-42).