Effects of short-term Western diet on cerebral oxidative stress and diabetes related factors in APPPS1 knock-in mice

• Published in: Journal of neurochemistry Vol. 108; no. 4; pp. 860 - 866
• Main Authors: Studzinski, Christa M, Li, Feng, Bruce-Keller, Annadora J, Fernandez-Kim, Sun Ok, Zhang, Le, Weidner, Adam M, Markesbery, William R, Murphy, MPaul, Keller, Jeffrey N
• Format: Journal Article
• Language: English
• Published: 01.02.2009
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2008.05798.x

AbstractA chronic high fat Western diet (WD) promotes a variety of morbidity factors although experimental evidence for short-term WD mediating brain dysfunction remains to be elucidated. The amyloid precursor protein and presenilin-1 (APPPS1) knock-in mouse model has been demonstrated to recapitulate some key features of Alzheimer's disease pathology, including amyloid- beta (A beta ) pathogenesis. In this study, we placed 1-month-old APPPS1 mice and non-transgenic littermates on a WD for 4weeks. The WD resulted in a significant elevation in protein oxidation and lipid peroxidation in the brain of APPPS1 mice relative to non-transgenic littermates, which occurred in the absence of increased A beta levels. Altered adipokine levels were also observed in APPPS1 mice placed on a short-term WD, relative to non-transgenic littermates. Taken together, these data indicate that short-term WD is sufficient to selectively promote cerebral oxidative stress and metabolic disturbances in APPPS1 knock-in mice, with increased oxidative stress preceding alterations in A beta . These data have important implications for understanding how WD may potentially contribute to brain dysfunction and the development of neurodegenerative disorders such as Alzheimer's disease.