Caffeine protects against MPTP-induced blood-brain barrier dysfunction in mouse striatum

Xuesong Chen, Xun Lan, Ian Roche, Rugao Liu, Jonathan Geiger

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

The blood-brain barrier (BBB) is important physiologically. Pathologically, BBB disruption has been implicated in a wide spectrum of neurological disorders including Parkinson's disease (PD). Recent studies indicate that caffeine is protective against PD, but by poorly understood mechanisms. Using a MPTP neurotoxin model of PD we tested the hypothesis that the protective actions of caffeine were because of, at least in part, preventing MPTP-induced BBB dysfunction. FVB mice were pre-treated with caffeine (10 mg/kg, i.p.) or saline for 7 days prior to initiation of neurotoxin treatments; during the 7 days of neurotoxin treatment, caffeine or saline continued to be administered 10 min before each dose of MPTP (20 mg/kg, i.p.). Striatum (and for some studies hippocampus and cerebral cortex as well) were evaluated for BBB leakage, tight junction protein expression levels, integrity of dopaminergic neurons, and activation of astrocytes and microglia using immunostaining, immunoblotting and real-time PCR techniques. We found that caffeine blocked MPTP-induced decreases in numbers of tyrosine hydroxylase-positive dopaminergic neurons, increases in leakage of Evan's blue dye and FITC-albumin in striatum but not in cerebral cortex or hippocampus, decreases in levels of the tight junction proteins occludin and ZO-1, and increases in reactive gliosis. Our results suggest that caffeine might protect against PD and PD-like features in animal models, in part, by stabilizing the BBB.

Original languageEnglish (US)
Pages (from-to)1147-1157
Number of pages11
JournalJournal of Neurochemistry
Volume107
Issue number4
DOIs
StatePublished - Nov 1 2008

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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Caffeine
Blood-Brain Barrier
Parkinson Disease
Neurotoxins
Tight Junction Proteins
Dopaminergic Neurons
Cerebral Cortex
Neurons
Hippocampus
Zonula Occludens-1 Protein
Occludin
Evans Blue
Gliosis
Tyrosine 3-Monooxygenase
Microglia
Nervous System Diseases
Immunoblotting
Astrocytes
Real-Time Polymerase Chain Reaction

Keywords

  • Astrocytes
  • Matrix metalloproteinase
  • Microglia
  • Parkinson's disease
  • Tight junction proteins

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Caffeine protects against MPTP-induced blood-brain barrier dysfunction in mouse striatum. / Chen, Xuesong; Lan, Xun; Roche, Ian; Liu, Rugao; Geiger, Jonathan.

In: Journal of Neurochemistry, Vol. 107, No. 4, 01.11.2008, p. 1147-1157.

Research output: Contribution to journalArticle

Chen, Xuesong ; Lan, Xun ; Roche, Ian ; Liu, Rugao ; Geiger, Jonathan. / Caffeine protects against MPTP-induced blood-brain barrier dysfunction in mouse striatum. In: Journal of Neurochemistry. 2008 ; Vol. 107, No. 4. pp. 1147-1157.
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