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


CONCLUSIONS
Nicotine moderately attenuated BBB disruption induced by chronic ingestion of high-SFA diet, but had no significant effect on neuroinflammation per se.
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.
Mina
M
Elahy
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;
Virginie
V
Lam
CHIRI Biosciences Research Precinct, Curtin Health Innovation Research Institute, Curtin University, Perth, Australia;
Menuka M
MM
Pallebage-Gamarallage
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;
Corey
C
Giles
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;
John C L
JC
Mamo
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; r.takechi@curtin.edu.au.
Ryusuke
R
Takechi
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D004041:Dietary Fats / Q000008:administration & dosage / Q000633:toxicity*; D005227:Fatty Acids / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000008:administration & dosage*
D004041:Dietary Fats; D005227:Fatty Acids; D009538:Nicotine