尼古丁减轻野生型小鼠饱和脂肪喂养诱导的血脑屏障破坏。

Nicotine Attenuates Disruption of Blood-Brain Barrier Induced by Saturated-Fat Feeding in Wild-Type Mice.

作者信息

Elahy Mina, Lam Virginie, Pallebage-Gamarallage Menuka M, Giles Corey, Mamo John C L, Takechi Ryusuke

机构信息

School of Public Health, Faculty of Health Sciences, Curtin University, Perth, Australia; CHIRI Biosciences Research Precinct, Curtin Health Innovation Research Institute, Curtin University, Perth, Australia; School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Perth, Australia.

出版信息

Nicotine Tob Res. 2015 Dec;17(12):1436-41. doi: 10.1093/ntr/ntv044. Epub 2015 Mar 5.

DOI:10.1093/ntr/ntv044

PMID:25744960

Abstract

INTRODUCTION

Emerging evidence suggests that integrity of blood-brain barrier (BBB) is pivotal to pathology and pathogenesis of vascular-based neurodegenerative disorders. We have recently reported BBB protective effects of nutraceutical agents with anti-inflammatory properties in an established dietary-induced BBB dysfunction model. Studies also reported that nicotine exhibits anti-oxidative/-inflammatory effects and improve cognitive impairment in Alzheimer's disease. However there has been no studies reporting the effect of nicotine on high-fat-induced BBB dysfunction.

METHODS

In the present study, we investigated the effect of nicotine on BBB integrity and neuro-inflammation in an established mouse model of BBB disruption induced by a diet enriched in saturated fatty acids (SFA).

RESULTS

Wild-type C57BL/6J mice were fed chow enriched in SFA (23% w/w) with/without nicotine for 10 weeks. Compared to mice maintained on SFA-free and low-fat (LF) chow (4% w/w), capillary permeability indicated by the parenchymal extravasation of plasma derived IgG, was significantly greater in the SFA treatment group. Nicotine provided concomitantly with the SFA diet significantly attenuated IgG extravasation, however it remained significantly greater than LF-controls. Markers of neurovascular inflammation glial fibrillary acidic protein, cyclooxygenase-2, and glucose regulated protein 78 remained exaggerated in SFA+nicotine treated mice compared to LF-controls. Nicotine did however modestly, but not significantly, improve plasma total anti-oxidative status in SFA fed mice.

CONCLUSION

Nicotine moderately attenuated BBB disruption induced by chronic ingestion of high-SFA diet, but had no significant effect on neuroinflammation per se.

摘要

引言

新出现的证据表明，血脑屏障（BBB）的完整性对于基于血管的神经退行性疾病的病理和发病机制至关重要。我们最近报道了在已建立的饮食诱导的血脑屏障功能障碍模型中，具有抗炎特性的营养剂对血脑屏障的保护作用。研究还报道，尼古丁具有抗氧化/抗炎作用，并可改善阿尔茨海默病中的认知障碍。然而，尚无研究报道尼古丁对高脂诱导的血脑屏障功能障碍的影响。

方法

在本研究中，我们在由富含饱和脂肪酸（SFA）的饮食诱导的已建立的血脑屏障破坏小鼠模型中，研究了尼古丁对血脑屏障完整性和神经炎症的影响。

结果

野生型C57BL/6J小鼠喂食富含SFA（23% w/w）的食物，添加或不添加尼古丁，持续10周。与喂食无SFA和低脂（LF）食物（4% w/w）的小鼠相比，血浆来源的IgG实质外渗所表明的毛细血管通透性在SFA治疗组中显著更高。与SFA饮食同时给予的尼古丁显著减轻了IgG外渗，然而，其仍显著高于LF对照组。与LF对照组相比，SFA+尼古丁处理的小鼠中神经血管炎症的标志物胶质纤维酸性蛋白、环氧化酶-2和葡萄糖调节蛋白78仍然过高。然而，尼古丁确实适度但不显著地改善了喂食SFA的小鼠的血浆总抗氧化状态。