Graham, Leah C.Grabowska, Weronika A.Chun, YoonaRisacher, Shannon L.Philip, Vivek M.Saykin, Andrew J.Sukoff Rizzo, Stacey J.Howell, Gareth R.2019-07-122019-07-122019-08Graham, L. C., Grabowska, W. A., Chun, Y., Risacher, S. L., Philip, V. M., Saykin, A. J., … Howell, G. R. (2019). Exercise prevents obesity-induced cognitive decline and white matter damage in mice. Neurobiology of Aging, 80, 154–172. https://doi.org/10.1016/j.neurobiolaging.2019.03.018https://hdl.handle.net/1805/19880Obesity in the western world has reached epidemic proportions, and yet the long-term effects on brain health are not well understood. To address this, we performed transcriptional profiling of brain regions from a mouse model of western diet (WD)-induced obesity. Both the cortex and hippocampus from C57BL/6J (B6) mice fed either a WD or a control diet from 2 months of age to 12 months of age (equivalent to midlife in a human population) were profiled. Gene set enrichment analyses predicted that genes involved in myelin generation, inflammation, and cerebrovascular health were differentially expressed in brains from WD-fed compared to control diet-fed mice. White matter damage and cerebrovascular decline were evident in brains from WD-fed mice using immunofluorescence and electron microscopy. At the cellular level, the WD caused an increase in the numbers of oligodendrocytes and myeloid cells suggesting that a WD is perturbing myelin turnover. Encouragingly, cerebrovascular damage and white matter damage were prevented by exercising WD-fed mice despite mice still gaining a significant amount of weight. Collectively, these data show that chronic consumption of a WD in B6 mice causes obesity, neuroinflammation, and cerebrovascular and white matter damage, but these potentially damaging effects can be prevented by modifiable risk factors such as exercise.enPublisher Policyagingbrain healthobesityArticle