Deleterious Effects of Minocycline in Animal Models of Parkinson’s Disease and Huntington’s Disease
Open accessAbstract
Minocycline has been shown to exert anti-inflammatory effects underlying its putative neuroprotective properties in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease and in the R6/2 mouse model of Huntington's disease (HD). However, contradictory results have recently been reported. We report deleterious effects of minocycline in two phenotypic (toxic) models of Parkinson's disease and HD in monkey and mouse. Of seven MPTP-intoxicated female cynomolgus monkeys (0.2 mg/kg, i.v. until day 15), three received minocycline (200 mg b.i.d.). While placebo-MPTP-treated animals displayed mild parkinsonism at day 15, the minocycline/MPTP-treated animals tended to be more affected (P = 0.057) and showed a greater loss of putaminal dopaminergic nerve endings (P < 0.0001). In the 3-nitropropionic acid (3-NP) mouse model of HD, minocycline (45 mg/kg i.p.) was administered 30 min before each i.p. injection of 3-NP (b.i.d., cumulated dose, 360 mg/kg in 5 days). Mice receiving minocycline exhibited a worsening of the mean motor score with a slower recovery slope, more impaired general activity and significantly deteriorated performances on the rotarod, pole test and beam-traversing tasks. The histopathological outcome demonstrated that minocycline-treated mice presented significantly more severe neuronal cell loss in the dorsal striatum. The effect of minocycline vs. 3-NP was also investigated on hippocampal and cortical cell cultures. minocycline blocked 3-NP-induced neurotoxicity at certain doses (1 mm cortical neurons) but not at higher doses (10 mm). Thus, minocycline may have variable and even deleterious effects in different species and models according to the mode of administration and dose.
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Minocycline administration to MPTP-treated rodents and primates causes enhanced toxicity and disease exacerbation.
“Indeed, an enhanced toxicity has been reported upon minocycline administration to MPTP-treated rodents and primates, resulting in disease exacerbation [275,276].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [276]
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- Authors
- Diguet, E., Fernagut, P., Wei, X., Du, Y., Rouland, R., Gross, C., Bezard, E., & Tison, F.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Indiana University School of Medicine (US)
- Corresponding author
- Tison, François
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2004-06
- Volume
- 19
- Issue
- 12
- Pages
- 3266-3276
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W1954166865
- Cited by
- 189
- References
- 67
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 2 · 2022: 6 · 2021: 18 · 2020: 8 · 2019: 9 · 2018: 7 · 2017: 5 · 2016: 7 · 2015: 7 · 2014: 5 · 2013: 12 · 2012: 14
- FWCI
- 10.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Association France Parkinson
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- minocycline, Parkinson's disease, Huntington's disease, MPTP-induced neurotoxicity, 3-nitropropionic acid, neuroprotection, neurotoxicity, parkinsonism, dopaminergic neuron loss, dorsal striatum, neuronal loss, hippocampal neurons, cortical neurons, dose-dependent effects, species differences, anti-inflammatory activity
- MeSH terms
- Animals, Cells, Cultured, Convulsants, Corpus Striatum, Disease Models, Animal, Female, Huntington Disease, Immunohistochemistry, Macaca fascicularis, Male, Minocycline, Nerve Degeneration, Neurons, Nitro Compounds, Propionates, Neuroprotective Agents, Parkinsonian Disorders, Mice
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