High-fat diet protects the blood-brain barrier in an Alzheimer's disease mouse model
| Autor: | Aviv Shish, Dana Atrakchi-Baranes, Sharone Naor, David Goez, Alicia Leikin-Frenkel, Shirin Elhaik Goldman, Michal Schnaider Beeri, Chen Shemesh, Yael Mardor, Rachel Twitto-Greenberg, Roni Lotan, Sigal Liraz Zaltsman, Shoval Tsach, Inbal Sharvit-Ginon, Itzik Cooper |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Aging Transcription Genetic Morris water navigation task Type 2 diabetes Anxiety blood–brain barrier 0302 clinical medicine insulin resistance Brain Short Take Organ Size Lipids medicine.anatomical_structure Blood-Brain Barrier Tg2576 mice Alzheimer’s disease MRI medicine.medical_specialty Genotype Amyloid beta Spatial Learning Mice Transgenic Biology Diet High-Fat Blood–brain barrier high‐fat diet 03 medical and health sciences Insulin resistance Atrophy Alzheimer Disease Internal medicine mental disorders medicine Animals Maze Learning Amyloid beta-Peptides cholesterol nutritional and metabolic diseases Lipid metabolism Cell Biology medicine.disease Receptor Insulin amyloid beta Disease Models Animal Insulin receptor 030104 developmental biology Endocrinology nervous system biology.protein 030217 neurology & neurosurgery |
| Zdroj: | Aging Cell |
| ISSN: | 1474-9718 |
| DOI: | 10.1111/acel.12818 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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