Protective Effect of Genistein against Neuronal Degeneration in ApoE−/− Mice Fed a High-Fat Diet
AbstractAltered cholesterol metabolism is believed to play a causal role in major pathophysiological changes in neurodegeneration. Several studies have demonstrated that the absence of apolipoprotein E (ApoE), a predominant apolipoprotein in the brain, leads to an increased susceptibility to neurodegeneration. Previously, we observed that genistein, a soy isoflavone, significantly alleviated apoptosis and tau hyperphosphorylation in SH-SY5Y cells. Therefore, we investigated the neuroprotective effects of dietary genistein supplementation (0.5 g/kg diet) in the cortex and hippocampus of wild-type C57BL/6 (WT) and ApoE knockout (ApoE−/−) mice fed a high-fat diet (HFD) for 24 weeks. Genistein supplementation alleviated neuroinflammation and peripheral and brain insulin resistance. Reductions in oxidative and endoplasmic reticulum stress were also observed in ApoE−/− mice fed a genistein-supplemented diet. Beta-secretase 1 and presenilin 1 mRNA levels and beta-amyloid peptide (Aβ) protein levels were reduced in response to genistein supplementation in ApoE−/− mice but not in WT mice. Although the absence of ApoE did not increase tau hyperphosphorylation, genistein supplementation reduced tau hyperphosphorylation in both WT and ApoE−/− mice. Consistent with this result, we also observed that genistein alleviated activity of c-Jun N-terminal kinase and glycogen synthase kinase 3β, which are involved in tau hyperphosphorylation. Taken together, these results demonstrate that genistein alleviated neuroinflammation, Aβ deposition, and hyperphosphorylation in ApoE−/− mice fed an HFD. View Full-Text
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Park, Y.-J.; Ko, J.W.; Jeon, S.; Kwon, Y.H. Protective Effect of Genistein against Neuronal Degeneration in ApoE−/− Mice Fed a High-Fat Diet. Nutrients 2016, 8, 692.
Park Y-J, Ko JW, Jeon S, Kwon YH. Protective Effect of Genistein against Neuronal Degeneration in ApoE−/− Mice Fed a High-Fat Diet. Nutrients. 2016; 8(11):692.Chicago/Turabian Style
Park, Yoon-Jin; Ko, Je W.; Jeon, Sookyoung; Kwon, Young H. 2016. "Protective Effect of Genistein against Neuronal Degeneration in ApoE−/− Mice Fed a High-Fat Diet." Nutrients 8, no. 11: 692.
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