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Proteasome inhibition in medaka brain induces the features of Parkinson’s disease
- Source :
- Journal of Neurochemistry. 115:178-187
- Publication Year :
- 2010
- Publisher :
- Wiley, 2010.
-
Abstract
- Recent findings suggest that a defect in the ubiquitin-proteasome system plays an important role in the pathogenesis of Parkinson's disease (PD). A previous report (McNaught et al. 2004) demonstrated that rats systemically injected with proteasome inhibitors exhibited PD-like clinical symptoms and pathology. However, because these findings have not been consistently replicated, this model is not commonly used to study PD. We used medaka fish to test the effect of systemic administration of proteasome inhibitors because of the high level of accessibility of the cerebrospinal fluid in fish. We injected lactacystin or epoxomicin into the CSF of medaka. With proteasome inhibition in the medaka brain, selective dopaminergic and noradrenergic cell loss was observed. Furthermore, treated fish exhibited reduced spontaneous movement. Treatment with proteasome inhibitors also induced the formation of inclusion bodies resembling Lewy bodies, which are characteristic of PD. Treatment with 6-OHDA also induced dopaminergic cell loss but did not produce inclusion bodies. These findings in medaka are consistent with previous results reporting that non-selective proteasome inhibition replicates the cardinal features of PD: locomotor dysfunction, selective dopaminergic cell loss, and inclusion body formation.
- Subjects :
- medicine.medical_specialty
Parkinson's disease
Lactacystin
Dopaminergic
Biology
medicine.disease
Biochemistry
Inclusion bodies
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Epoxomicin
Endocrinology
chemistry
Proteasome
Internal medicine
Dopaminergic Cell
medicine
Proteasome inhibitor
medicine.drug
Subjects
Details
- ISSN :
- 00223042
- Volume :
- 115
- Database :
- OpenAIRE
- Journal :
- Journal of Neurochemistry
- Accession number :
- edsair.doi...........0bb73c64ea03cc96723c91c1461d30f0