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Genistein alleviates neurodegeneration in ApoE −/− mice fed a high‐fat diet
Author(s) -
Kwon Young Hye,
Park YounJin,
Jeon Sookyoung
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.861.22
Subject(s) - neurodegeneration , endocrinology , medicine , apolipoprotein e , neuroprotection , hyperphosphorylation , neurotoxicity , apoptosis , biology , kinase , chemistry , toxicity , biochemistry , disease
Altered cholesterol metabolism is believed to play a causal role in major pathophysiological changes in neurodegeneration. Several studies have shown that absence of ApoE leads to an increased susceptibility to neurodegeneration by influencing metabolism of beta‐amyloid peptide and tau protein. Previously, we observed that genistein (GEN) significantly alleviated apoptosis and tau hyperphosphorylation in db/db mice fed a methionine‐choline deficient diet and in SH‐SY5Y neuroblastoma cells. Therefore, we investigated neuroprotective effects of GEN in ApoE −/− mice fed a high‐fat diet (HFD). Both WT and ApoE −/− mice were fed either an HFD with or without with GEN (0.5 g/kg diet) for 24 wk. Although ApoE −/− mice fed an HFD did not exhibit a significantly increased tau hyperphosphorylation compared to WT mice, GEN supplementation significantly reduced tau hyperphosphorylation in the cortex and hippocampus of both genotypes. Consistently, we observed that GEN significantly inhibited activities of JNK and GSK3‐β, kinases involved in tau phosphorylation. Significantly lower levels of apoptosis were also observed in response to GEN supplementation. Therefore, these results demonstrate that GEN may alleviate neurodegeneration in both WT and ApoE −/− mice fed an HFD. This work was supported by National Research Foundation of Korea.