Premium
Caffeine blocks MPTP‐induced increases in blood‐brain barrier leakage in mouse striatum
Author(s) -
Chen Xuesong,
Lan Xun,
Liu Rugao,
Geiger Jonathan D.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.734.14
Subject(s) - mptp , dopaminergic , striatum , occludin , blood–brain barrier , neuroinflammation , astrocytosis , parkinson's disease , neurotoxin , cerebral cortex , caffeine , medicine , pharmacology , neuroscience , chemistry , endocrinology , dopamine , central nervous system , tight junction , biology , biochemistry , disease
The blood‐brain barrier (BBB) is important physiologically, and pathologically BBB disruption has been implicated in a wide spectrum of neurological disorders including Parkinson's disease. Recent studies indicate that caffeine is protective against Parkinson's disease, but by poorly understood mechanisms. Using a MPTP neurotoxin model of Parkinson's disease, we tested the hypothesis that caffeine protects against MPTP‐induced BBB leakage. FVB mice were pretreated with caffeine (10 mg/kg, i.p.) or saline 10 min before each dose of MPTP (20 mg/kg, i.p.) or saline for 7 days. Striatum (and for some studies hippocampus and cerebral cortex as well) were evaluated for BBB leakage, tight junction protein expression, presence of dopaminergic neurons, and neuroinflammation by immunostaining, immunoblotting or real‐time PCR techniques. We found that caffeine blocked MPTP‐induced decreases in TH‐positive dopaminergic neurons, increases in leakage of Evan's blue dye specifically in stratum but not in cerebral cortex or hippocampus, decreases in levels of the tight junction proteins occludin, claudin‐5 and ZO‐1, and increases in reactive astrocytosis. Our results suggest that caffeine might protect against Parkinson's disease, in part, by stabilizing the BBB. (Supported by P20 RR‐017699 from the NCRR, a component of the NIH)