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Publication : High-fat diet protects the blood-brain barrier in an Alzheimer's disease mouse model.

First Author  Elhaik Goldman S Year  2018
Journal  Aging Cell Volume  17
Issue  5 Pages  e12818
PubMed ID  30079520 Mgi Jnum  J:265426
Mgi Id  MGI:6200472 Doi  10.1111/acel.12818
Citation  Elhaik Goldman S, et al. (2018) High-fat diet protects the blood-brain barrier in an Alzheimer's disease mouse model. Aging Cell 17(5):e12818
abstractText  Type 2 diabetes (T2D) is associated with increased risk of Alzheimer's disease (AD). There is evidence for impaired blood-brain barrier (BBB) in both diseases, but its role in the interplay between them is not clear. Here, we investigated the effects of high-fat diet (HFD), a model for T2D, on the Tg2576 mouse model of AD, in regard to BBB function. We showed that HFD mice had higher weight, more insulin resistance, and higher serum HDL cholesterol levels, primarily in Tg2576 mice, which also had higher brain lipids content. In terms of behavior, Tg2576 HFD mice were less active and more anxious, but had better learning in the Morris Water Maze compared to Tg2576 on regular diet. HFD had no effect on the level of amyloid beta 1-42 in the cortex of Tg2576 mice, but increased the transcription level of insulin receptor in the hippocampus. Tg2576 mice on regular diet demonstrated more BBB disruption at 8 and 12 months accompanied by larger lateral ventricles volume in contrast to Tg2576 HFD mice, whose BBB leakage and ventricular volume were similar to wild-type (WT) mice. Our results suggest that in AD, HFD may promote better cognitive function through improvements of BBB function and of brain atrophy but not of amyloid beta levels. Lipid metabolism in the CNS and peripheral tissues and brain insulin signaling may underlie this protection.
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