Protective Effect of Genistein against Neuronal Degeneration in ApoE-/-Mice Fed a High-Fat Diet.
Altered 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) andApoEknockout (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 inApoE-/-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 inApoE-/-mice but not in WT mice. Although the absence ofApoEdid not increase tau hyperphosphorylation, genistein supplementation reduced tau hyperphosphorylation in both WT andApoE-/-mice. Consistent with this result, we also observed that genistein alleviated activity of c-JunN-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 inApoE-/-mice fed an HFD.
Department of Food and Nutition, Seoul National University, Seoul 08826, Korea. younjjn@snu.ac.kr.
Yoon-Jin
YJ
Park
Department of Food and Nutition, Seoul National University, Seoul 08826, Korea. kgrami@snu.ac.kr.
Je Won
JW
Ko
Department of Food and Nutition, Seoul National University, Seoul 08826, Korea. sookyoung.jeon@gmail.com.
Sookyoung
S
Jeon
Department of Food and Nutition, Seoul National University, Seoul 08826, Korea. hye0414@snu.ac.kr.|Research Institute of Human Ecology, Seoul National University, Seoul 08826, Korea. hye0414@snu.ac.kr.
Young Hye
YH
Kwon
D000544:Alzheimer Disease / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use; D000975:Antioxidants / Q000009:adverse effects / Q000627:therapeutic use; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002540:Cerebral Cortex / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects; D019587:Dietary Supplements; D059865:Endoplasmic Reticulum Stress; D005786:Gene Expression Regulation; D019833:Genistein / Q000009:adverse effects / Q000627:therapeutic use*; D006624:Hippocampus / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018384:Oxidative Stress; D053764:Presenilin-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001057:Apolipoproteins E; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D053764:Presenilin-1; C580804:presenilin 1, mouse; D019833:Genistein; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse
ApoE−/− mice; brain; genistein; neurodegeneration; neuroinflammation