Metallothionein synthesis increased by Ninjin-yoei-to, a Kampo medicine protects neuronal death and memory loss after exposure to amyloid ß1-42.

BACKGROUND: It is possible that increased synthesis of metallothioneins (MTs), Zn2+-binding proteins is linked with the protective effect of Ninjin-yoei-to (NYT) on Zn2+ toxicity ferried by amyloid ß1-42 (Aß1-42). METHODS: Judging from the biological half-life (18-20 h) of MTs, the effective period of newly synthesized MT on capturing Zn2+ 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 Aß1-42 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 Zn2+ level increased 1 h after Aß1-42 injection, resulting in rescuing neuronal death in the dentate granule cell layer, which was observed 14 days after Aß1-42 injection. Furthermore, Pre-administration of NYT diet rescued object recognition memory loss via affected perforant pathway long-term potentiation after local injection of Aß1-42 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 Zn2+ toxicity ferried by extracellular Aß1-42, resulting in protecting neuronal death in the dentate gyrus and memory loss after exposure to Aß1-42.

Photo-induced in situ crosslinking of polymer brushes with dimethyl maleimide moieties for dynamically stimulating stem cell differentiation.

We designed photo-crosslinkable polymer brushes with dimethylmaleimide moieties, in order to demonstrate dynamic stimulation of cell differentiation in mesenchymal stem cells (MSCs). The polymer brushes were synthesized by surface-initiated reversible addition fragmentation chain transfer polymerization using dimethylmaleimide ethyl methacrylate and methyl methacrylate on a chain transfer agent-immobilized glass surface. The polymer brushes were crosslinked by photodimerization of the dimethylmaleimide moieties within polymer chains with stem cells present on the surface. In order to evaluate the effects of in situ photo-induced crosslinking of the polymer brushes on gene expression of stem cells, human bone marrow MSCs were cultured under static and dynamic culture conditions for 7 days. Expression of the osteocalcin (Ocn) gene in MSCs was used as an indicator of osteoblast differentiation under dynamic culture conditions. Structural conversion from non-crosslinked polymer brushes to crosslinked polymer brushes increased the expression of Ocn by 1.4-fold in the presence of adhered cells, compared with non-crosslinked polymer brushes under static culture conditions. These results suggest that MSCs recognized surface conversion from non-crosslinked to crosslinked structures, which resulted in altered differentiation lineages. Therefore, photo-crosslinkable surfaces with dimethyl maleimide moieties are potential novel materials for dynamically stimulating MSC differentiation.