The MPTP-induced parkinsonian syndrome in the goldfish is associated with major cell destruction in the forebrain and subtle changes in the optic tectum.
The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can induce a parkinsonian syndrome in humans and nonhuman primates, which is susceptible to treatment and prevention by drugs such as L-DOPA and L-deprenyl. Recently, we have reported that MPTP can also cause a parkinsonian syndrome in the common goldfish, which appears to faithfully mirror the neurochemical and behavioral aspects of the action of MPTP in the higher vertebrates. In addition, we recently identified the likely teleost equivalent of the substantia nigra in the goldfish forebrain, the "nucleus pars medialis," on the basis of its destruction by MPTP and selective protection by the MAO-B blocker L-deprenyl. In the present work we substantiate this conclusion by examining tissue destruction the goldfish forebrain at increasing MPTP concentrations, up to the the LD50 of 200 mg/kg. In addition, we show that at the highest MPTP dose subtle changes also occur with low frequency in nondopaminergic cells in the optic tectum, and in ependymal cells lining the midbrain ventricle. The effects on ependymal cells are similar to those previously noted in the forebrain. We conclude that the goldfish model continues to faithfully mimic the histologic pattern of parkinsonian tissue destruction engendered by MPTP in primate models.
Laboratory of Cell Biology and Genetics, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.
H B
HB
Pollard
G A
GA
Kuijpers
O M
OM
Adeyemo
M B
MB
Youdim
G
G
Goping
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002451:Cell Compartmentation / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D004298:Dopamine / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006054:Goldfish / Q000502:physiology*; D008854:Microscopy, Electron; D009475:Neurons, Afferent / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000473:pathology*; D016548:Prosencephalon / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D013477:Superior Colliculi / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D014795:Visual Pathways / Q000187:drug effects
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine