Resveratrol Attenuates High-Fat Diet-Induced Disruption of the Blood–Brain Barrier and Protects Brain Neurons from Apoptotic Insults

The blood–brain barrier (BBB) maintains brain microenvironment. Our previous study showed that oxidized low-density lipoprotein (oxLDL) can damage the BBB by inducing apoptosis of cerebrovascular endothelial cells. This study was aimed at evaluating the effects of resveratrol on high-fat diet-induce...

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Bibliographic Details
Published in:Journal of agricultural and food chemistry 2014-04, Vol.62 (15), p.3466-3475
Main Authors: Chang, Huai-Chia, Tai, Yu-Ting, Cherng, Yih-Giun, Lin, Jia-Wei, Liu, Shing-Hwa, Chen, Ta-Liang, Chen, Ruei-Ming
Format: Article
Language:English
Subjects:
Animals
apoptosis
Apoptosis - drug effects
blood serum
blood-brain barrier
Blood-Brain Barrier - drug effects
Blood-Brain Barrier - metabolism
brain
Brain - cytology
Brain - drug effects
Brain - metabolism
caspase-3
cholesterol
death
Diet, High-Fat - adverse effects
Dietary Fats - metabolism
DNA
DNA fragmentation
endothelial cells
high fat diet
Humans
Intracranial Arteriosclerosis - drug therapy
Intracranial Arteriosclerosis - metabolism
Intracranial Arteriosclerosis - physiopathology
Intracranial Arteriosclerosis - prevention & control
low density lipoprotein
Male
Mice
Mice, Inbred ICR
neurons
Neurons - cytology
Neurons - drug effects
Neurons - metabolism
occludins
permeability
polymerization
resveratrol
Stilbenes - administration & dosage
tight junctions
tissues
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Summary:The blood–brain barrier (BBB) maintains brain microenvironment. Our previous study showed that oxidized low-density lipoprotein (oxLDL) can damage the BBB by inducing apoptosis of cerebrovascular endothelial cells. This study was aimed at evaluating the effects of resveratrol on high-fat diet-induced insults to the BBB and brain neurons. Exposure of mice to a high-fat diet for 8 weeks increased levels of serum total cholesterol (146 ± 13) and LDL (68 ± 8), but resveratrol decreased such augmentations (119 ± 6; 45 ± 8). Permeability assays showed that a high-fat diet induced breakage of the BBB (88 ± 21). Meanwhile, resveratrol alleviated this interruption (16 ± 6). Neither resveratrol nor a high-fat diet caused the death of cerebrovascular endothelial cells. Instead, exposure to a high-fat diet disrupted the polymerization of occludin and zonula occludens (ZO)-1, but resveratrol significantly attenuated those injuries. Neither a high-fat diet nor resveratrol changed the levels of occludin or ZO-1 in brain tissues. Resveratrol protected brain neurons against high-fat diet-induced caspase-3 activation and genomic DNA fragmentation. This study shows that resveratrol can attenuate the high-fat diet-induced disruption of the BBB via interfering with occludin and ZO-1 tight junctions, and protects against apoptotic insults to brain neurons.
ISSN:0021-8561
1520-5118
DOI:10.1021/jf403286w