Caffeine protects against MPTP‐induced blood‐brain barrier dysfunction in mouse striatum
Open accessAbstract
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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Reduced expression of tight junction proteins has been shown in MPTP Parkinson's disease models.
“Reduced expression of TJ proteins has also been shown in MPTP PD models (108).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [108]
In rodent models of Parkinson's disease induced by MPTP or 6-OHDA, compromised blood-brain barrier integrity is observed, including leakage of FITC-albumin, horseradish peroxidase, and Evan's blue in the substantia nigra and striatum.
“compromised BBB integrity is also observed in rodent models of PD induced by systemic administration of MPTP (108, 680) or intrastriatal administration of 6-hydroxydopamine (6-OHDA) (95), including leakage of fluoresceinisothiocyanate (FITC)-labeled albumin (95, 108, 680), horseradish peroxidase (95), and Evan's blue (108) in the substantia nigra and striatum.”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [108]
Nigrostriatal vascular leakage has been reported in MPTP-treated mice.
“nigrostriatal vascular leakage has been reported in MPTP-treated mice [73]”
From Healthy Human Fecal Microbiota Transplantation into Mice Attenuates MPTP-Induced Neurotoxicity <i>via</i> AMPK/SOD2 Pathway (2023) · cites this paper as [73]
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- Authors
- Chen, X., Lan, X., Roche, I., Liu, R., & Geiger, J. D.
- Affiliations
- University of North Dakota (US)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2008-10-21
- Volume
- 107
- Issue
- 4
- Pages
- 1147-1157
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- 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
- 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 › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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