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-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.
Graduate Institute of Medical Sciences, Taipei Medical University; Comprehensive Cancer Center of Taipei Medical University , Taipei 11031, Taiwan.
Huai-Chia
HC
Chang
Yu-Ting
YT
Tai
Yih-Giun
YG
Cherng
Jia-Wei
JW
Lin
Shing-Hwa
SH
Liu
Ta-Liang
TL
Chen
Ruei-Ming
RM
Chen
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000378:metabolism; D006801:Humans; D002537:Intracranial Arteriosclerosis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage*
D004041:Dietary Fats; D013267:Stilbenes; D000077185:Resveratrol