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Proteasome inhibition in medaka brain induces the features of Parkinson’s disease
Author(s) -
Matsui Hideaki,
Ito Hidefumi,
Taniguchi Yoshihito,
Inoue Haruhisa,
Takeda Shunichi,
Takahashi Ryosuke
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06918.x
Subject(s) - lactacystin , proteasome , dopaminergic , proteasome inhibitor , parkinson's disease , inclusion bodies , biology , pathogenesis , dementia with lewy bodies , neurodegeneration , oryzias , ubiquitin , dopamine , medicine , microbiology and biotechnology , neuroscience , endocrinology , disease , biochemistry , immunology , gene , dementia , escherichia coli
J. Neurochem. (2010) 115 , 178–187. 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.