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

Tamano, Haruna; Takiguchi, Mako; Saeki, Nana; Katahira, Misa; Shioya, Aoi; Tanaka, Yukino; Egawa, Mako; Fukuda, Takuya; Ikeda, Hiroki; Takeda, Atsüshi

doi:10.1007/s12035-021-02364-3

Cited by 7 publications

(1 citation statement)

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“…Aβ 1-42 readily captures Zn 2+ in the extracellular fluid and Zn-Aβ 1-42 complexes are preferentially taken up into dentate gyrus neurons, resulting in cognitive impairment and neuronal death, which are linked with intracellular Zn 2+ toxicity ferried by Aβ 1-42 [ 5 – 7 ]. The protection of dentate gyrus neurons against Zn 2+ toxicity is a potential target to protect the Aβ 1-42 -mediated pathogenesis [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Metallothionein synthesis increased by Ninjin-yoei-to, a Kampo medicine protects neuronal death and memory loss after exposure to amyloid β1-42

Tamano

Tokoro

Murakami

et al. 2022

J Pharm Health Care Sci

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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 β1-42 (Aβ1-42). 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 Aβ1-42 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 Aβ1-42 injection, resulting in rescuing neuronal death in the dentate granule cell layer, which was observed 14 days after Aβ1-42 injection. Furthermore, Pre-administration of NYT diet rescued object recognition memory loss via affected perforant pathway long-term potentiation after local injection of Aβ1-42 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 Aβ1-42, resulting in protecting neuronal death in the dentate gyrus and memory loss after exposure to Aβ1-42.

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