Exercise prevents obesity-induced cognitive decline and white matter damage in mice

• Published in: Neurobiology of aging 2019-08, Vol.80, p.154-172
• Main Authors: Graham, Leah C., Grabowska, Weronika A., Chun, Yoona, Risacher, Shannon L., Philip, Vivek M., Saykin, Andrew J., Sukoff Rizzo, Stacey J., Howell, Gareth R.
• Format: Article
• Language: English
• Subjects: Aging; Animals; Brain Health; Cerebrovascular Health; Cognitive Dysfunction - etiology; Cognitive Dysfunction - prevention & control; Exercise; Exercise - physiology; Humans; Inflammation; Leukoencephalopathies - pathology; Leukoencephalopathies - prevention & control; Mice, Inbred C57BL; Neuroinflammation; Obesity; Obesity - complications; Obesity - prevention & control; Oligodendroglia - pathology; Physical Conditioning, Animal - physiology; White Matter - cytology; White Matter - pathology
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2019.03.018

Obesity 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. •White matter damage is present in both humans and mouse models of obesity.•Myeloid cells increase in white matter regions in western diet (WD)-fed obese mice.•Blood-brain barrier dysfunction occurs in WD-fed obese mice.•Voluntary running prevented damaging effects of a WD.