title: Susceptibility to a parkinsonian toxin varies during primate development.
abstract: Symptoms of Parkinson's disease typically emerge later in life when loss of nigrostriatal dopamine neuron function exceeds the threshold of compensatory mechanisms in the basal ganglia. Although nigrostriatal dopamine neurons are lost during aging, in Parkinson's disease other detrimental factors must play a role to produce greater than normal loss of these neurons. Early development has been hypothesized to be a potentially vulnerable period when environmental or genetic abnormalities may compromise central dopamine neurons. This study uses a specific parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), to probe the relative vulnerability of nigrostriatal dopamine neurons at different stages of primate development. Measures of dopamine, homovanillic acid, 1-methyl-pyridinium concentrations and tyrosine hydroxylase immunoreactive neurons indicated that at mid-gestation dopamine neurons are relatively vulnerable to MPTP, whereas later in development or in the young primate these neurons are resistant to the neurotoxin. These studies highlight a potentially greater risk to the fetus of exposure during mid-gestation to environmental agents that cause oxidative stress. In addition, the data suggest that uncoupling protein-2 may be a target for retarding the progressive loss of nigrostriatal dopamine neurons that occurs in Parkinson's disease and aging.
authors.affiliation: Neuropsychopharmacology Research Laboratory, Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Morrow
authors.forename: R H
authors.initials: RH
authors.lastname: Roth
authors.forename: D E
authors.initials: DE
authors.lastname: Redmond
authors.forename: S
authors.initials: S
authors.lastname: Diano
authors.forename: J D
authors.initials: JD
authors.lastname: Elsworth
mesh_terms: D000367:Age Factors; D000818:Animals; D002522:Chlorocebus aethiops; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D020267:MPTP Poisoning / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid