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Cited by 68Parkinson's Disease Mechanisms and TreatmentsZebrafish Biomedical Research ApplicationsNuclear Receptors and Signaling

Neuroprotective and Neuro-Restorative Effects of Minocycline and Rasagiline in a Zebrafish 6-Hydroxydopamine Model of Parkinson’s Disease

Cronin, Aileen, Grealy, Maura·2017·Neuroscience
DOI 10.1016/j.neuroscience.2017.10.018
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Abstract

Parkinson's disease is a common, debilitating, neurodegenerative disorder for which the current gold standard treatment, levodopa (L-DOPA) is symptomatic. There is an urgent, unmet need for neuroprotective or, ideally, neuro-restorative drugs. We describe a 6-hydroxydopamine (6-OHDA) zebrafish model to screen drugs for neuroprotective and neuro-restorative capacity. Zebrafish larvae at two days post fertilization were exposed to 6-OHDA for three days, with co-administration of test drugs for neuroprotection experiments, or for 32 h, with subsequent treatment with test drugs for neuro-restoration experiments. Locomotor activity was assessed by automated tracking and dopaminergic neurons were visualized by tyrosine hydroxylase immuno-histochemistry. Exposure to 6-OHDA for either 32 h or 3 days induced similar, significant locomotor deficits and neuronal loss in 5-day-old larvae. L-DOPA (1 mM) partially restored locomotor activity, but was neither neuroprotective nor neuro-restorative, mirroring the clinical situation. The calcium channel blocker, isradipine (1 µM) did not prevent or reverse 6-OHDA-induced locomotor deficit or neuronal loss. However, both the tetracycline analog, minocycline (10 µM), and the monoamine oxidase B inhibitor, rasagiline (1 µM), prevented the locomotor deficits and neuronal loss due to three-day 6-OHDA exposure. Importantly, they also reversed the locomotor deficit caused by prior exposure to 6-OHDA; rasagiline also reversed neuronal loss and minocycline partially restored neuronal loss due to prior 6-OHDA, making them candidates for investigation as neuro-restorative treatments for Parkinson's disease. Our findings in zebrafish reflect preliminary clinical findings for rasagiline and minocycline. Thus, we have developed a zebrafish model suitable for high-throughput screening of putative neuroprotective and neuro-restorative therapies for the treatment of Parkinson's disease.

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  • Minocycline molecular changes explain increased striatal dopamine levels and cognitive and locomotor improvements in zebrafish, mouse, and rat models.

    “Of note, these molecular changes seem to explain the increased striatal dopamine levels as well as the cognitive and locomotor improvements observed in zebrafish, mouse, and rat models [259,260,264,268,269,270,271].”

    From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [268]

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Authors
Cronin, A., & Grealy, M.
Affiliations
Ollscoil na Gaillimhe – University of Galway (IE)
Corresponding author
Grealy, Maura
ORCID
Grealy, Maura
Venue
Neuroscience
Publisher
Elsevier BV
Published
2017-12
Volume
367
Pages
34-46
ISSN
0306-4522 (ISSN-L)
DOI
10.1016/j.neuroscience.2017.10.018
OpenAlex
W2765536831
Cited by
68
References
78
Citations by year
2026: 1 · 2025: 7 · 2024: 1 · 2023: 9 · 2022: 13 · 2021: 11 · 2020: 15 · 2019: 8 · 2018: 3
FWCI
4.95
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Funders
National University of Ireland, Galway
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
Parkinson's disease, minocycline, rasagiline, 6-hydroxydopamine, zebrafish model, neuroprotection, neurorestoration, dopaminergic neurons, locomotor deficits, neuronal loss, levodopa, isradipine, monoamine oxidase B inhibitors, calcium channel blockers, high-throughput drug screening
MeSH terms
Analysis of Variance, Animals, Disease Models, Animal, Drug Administration Schedule, Embryo, Nonmammalian, Indans, Levodopa, Locomotion, Minocycline, Parkinson Disease, Time Factors, Tyrosine 3-Monooxygenase, Zebrafish, Oxidopamine, Isradipine, Adrenergic Agents, Neuroprotective Agents, Dopaminergic Neurons

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