1. Dehydroeffusol Pprevents Amyloid β1-42-mediated Hippocampal Neurodegeneration via Reducing Intracellular Zn2+ Toxicity
- Author
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Atsushi Takeda, Yukino Tanaka, Mako Egawa, Aoi Shioya, Misa Katahira, Mako Takiguchi, Hiroki Ikeda, Nana Saeki, Toshiyuki Fukuda, and Haruna Tamano
- Subjects
0301 basic medicine ,Amyloid ,Chemistry ,Neurodegeneration ,Neuroscience (miscellaneous) ,Hippocampus ,Pharmacology ,Hippocampal formation ,medicine.disease ,Granule cell ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Neurology ,Oral administration ,Toxicity ,medicine ,030217 neurology & neurosurgery ,Intracellular - Abstract
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 β1-42 (Aβ1-42)-mediated hippocampal neurodegeneration. Dehydroeffusol (15 mg/kg body weight) was orally administered to mice once a day for 6 days and then human Aβ1-42 was injected intracerebroventricularly followed by oral administration for 12 days. Neurodegeneration in the dentate granule cell layer, which was determined 2 weeks after Aβ1-42 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 Zn2+ induced with Aβ1-42 was reduced, suggesting that pre-administration of dehydroeffusol prior to Aβ1-42 injection is effective for Aβ1-42-mediated neurodegeneration that was linked with intracellular Zn2+ toxicity. As a matter of fact, pre-administration of dehydroeffusol rescued Aβ1-42-mediated neurodegeneration. Interestingly, pre-administration of dehydroeffusol increased synthesis of metallothioneins, intracellular Zn2+-binding proteins, in the dentate granule cell layer, which can capture Zn2+ from Zn-Aβ1-42 complexes. The present study indicates that pre-administration of dehydroeffusol protects Aβ1-42-mediated neurodegeneration in the hippocampus by reducing intracellular Zn2+ toxicity, which is linked with induced synthesis of metallothioneins. Dehydroeffusol, a novel inducer of metallothioneins, may protect Aβ1-42-induced pathogenesis in Alzheimer's disease.
- Published
- 2021