Journal Article

Dehydroeffusol Pprevents Amyloid β1-42-mediated Hippocampal Neurodegeneration via Reducing Intracellular Zn2+ Toxicity

Takeda, Atsushi, Tamano, Haruna, Tanaka, Yukino, Egawa, Mako, Shioya, Aoi, Ikeda, Hiroki, Saeki, Nana, Katahira, Misa, Takiguchi, Mako, Fukuda, Toshiyuki

2021

Overview

Dehydroeffusol, a phenanthrene isolated from Juncus effusus , is a Chinese medicine. To explore an efficacy of dehydroeffusol administration for prevention and cure of Alzheimer’s disease, here we examined the effect of dehydroeffusol on amyloid β 1-42 (Aβ 1-42 )-mediated hippocampal neurodegeneration . Dehydroeffusol (15 mg/kg body weight) was orally administered to mice once a day for 6 days and then human Aβ 1-42 was injected intracerebroventricularly followed by oral administration for 12 days. Neurodegeneration in the dentate granule cell layer, which was determined 2 weeks after Aβ 1-42 injection, was rescued by dehydroeffusol administration. Aβ staining (uptake) was not reduced in the dentate granule cell layer by pre-administration of dehydroeffusol for 6 days, while increase in intracellular Zn 2+ induced with Aβ 1-42 was reduced, suggesting that pre-administration of dehydroeffusol prior to Aβ 1-42 injection is effective for Aβ 1-42 -mediated neurodegeneration that was linked with intracellular Zn 2+ toxicity. As a matter of fact, pre-administration of dehydroeffusol rescued Aβ 1-42 -mediated neurodegeneration. Interestingly, pre-administration of dehydroeffusol increased synthesis of metallothioneins, intracellular Zn 2+ -binding proteins, in the dentate granule cell layer, which can capture Zn 2+ from Zn-Aβ 1-42 complexes. The present study indicates that pre-administration of dehydroeffusol protects Aβ 1-42 -mediated neurodegeneration in the hippocampus by reducing intracellular Zn 2+ toxicity, which is linked with induced synthesis of metallothioneins. Dehydroeffusol, a novel inducer of metallothioneins, may protect Aβ 1-42 -induced pathogenesis in Alzheimer’s disease.

• Publisher: Springer US,Springer Nature B.V
• Subject: Alzheimer's disease / Amyloid / Biomedical and Life Sciences / Biomedicine / Body weight / Cell Biology / Hippocampus / Injection / Intracellular / Neurobiology / Neurodegeneration / Neurodegenerative diseases / Neurology / Neurosciences / Oral administration / Phenanthrene / Toxicity / Zinc