Cited by 189Barrier Structure and Function StudiesParkinson's Disease Mechanisms and TreatmentsNuclear Receptors and Signaling

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

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Chen, Xuesong, Lan, Xun, Roche, Ian, Liu, Rugao, Geiger, Jonathan D.·2008·Journal of Neurochemistry

DOI 10.1111/j.1471-4159.2008.05697.xPMC PMC3692355

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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.

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Authors: Chen, X., Lan, X., Roche, I., Liu, R., & Geiger, J. D.
Affiliations: University of North Dakota (US)
ORCID: Chen, Xuesong
Geiger, Jonathan D.
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 2008-10-21
Volume: 107
Issue: 4
Pages: 1147-1157
ISSN: 0022-3042 (ISSN-L)
1471-4159
DOI: 10.1111/j.1471-4159.2008.05697.x
PMC: PMC3692355
OpenAlex: W2006684548
Cited by: 189
References: 71
Citations by year: 2026: 7 · 2025: 9 · 2024: 12 · 2023: 18 · 2022: 11 · 2021: 14 · 2020: 13 · 2019: 11 · 2018: 7 · 2017: 9 · 2016: 13 · 2015: 11 · 2014: 10 · 2013: 10 · 2012: 9
FWCI: 5.47
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Neurochemistry (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Center for Research Resources (P20RR17699, P20RR017699)
Topics: Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Keywords: caffeine, MPTP, blood-brain barrier dysfunction, Parkinson's disease, striatum, tight junction proteins, occludin, ZO-1, dopaminergic neurons, tyrosine hydroxylase, reactive gliosis, astrocytes, microglia, neuroprotection, neurotoxicity
MeSH terms: Central Nervous System Stimulants, Analysis of Variance, Animals, Blood-Brain Barrier, Caffeine, Corpus Striatum, Disease Models, Animal, Evans Blue, Gene Expression Regulation, Gliosis, Male, Membrane Proteins, Phosphoproteins, RNA, Messenger, Tyrosine 3-Monooxygenase, MPTP Poisoning, Matrix Metalloproteinase 9, Mice, Occludin, Zonula Occludens-1 Protein

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

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