title: A chemical neurotoxin, MPTP induces Parkinson's disease like phenotype, movement disorders and persistent loss of dopamine neurons in medaka fish.
abstract: Parkinson's disease (PD) is the second most common neurodegenerative disease associated with the degeneration of dopaminergic neurons in the substantia nigra. To create a new model of PD, we used medaka (Oryzias latipes), a small teleost that has been used in genetics and environmental biology. We identified tyrosine hydroxylase (TH) immunopositive dopaminergic and noradrenergic fibers and neurons in the medaka brain. Following establishment of a method for counting the number of dopaminergic neurons and an assay for the evaluation of the medaka behavior, we exposed medaka to 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP). The treatment of medaka at the larval stage, but not at adult stage, decreased the number of dopaminergic cells in the diencephalon and reduced spontaneous movement, which is reminiscent of human PD patients and other MPTP-induced animal PD models. Among TH(+) neurons in the medaka brain, only a specific cluster in the paraventricular area of the middle diencephalon was vulnerable to MPTP toxicity. Detailed examinations of medaka transiently exposed to MPTP at the larval stage revealed that the number of dopaminergic cells was not fully recovered at their adult stage. Moreover, the amounts of dopamine persistently decreased in the brain of these MPTP-treated fish. MPTP-treated medaka is valuable for modeling human PD.
authors: Department of Neurology, Kyoto University, Graduate School of Medicine, Kyoto 606-8507, Japan.
authors: Hideaki
authors: H
authors: Matsui
authors: Yoshihito
authors: Y
authors: Taniguchi
authors: Haruhisa
authors: H
authors: Inoue
authors: Kengo
authors: K
authors: Uemura
authors: Shunichi
authors: S
authors: Takeda
authors: Ryosuke
authors: R
authors: Takahashi
mesh_terms: D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D004027:Diencephalon / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007814:Larva / Q000187:drug effects / Q000254:growth & development; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009990:Oryzias / Q000502:physiology*; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013995:Time
chemical_list: D015415:Biomarkers; D004298:Dopamine