title: Differential survival patterns among midbrain dopaminergic cells of MPTP-treated monkeys and 6OHDA-lesioned rats.
abstract: We explore the patterns of survival among dopaminergic cells of the midbrain in MPTP-treated macaque monkeys and 6OHDA-lesioned Sprague-Dawley rats. For the monkeys, animals were injected intramuscularly with MPTP for 8 days consecutively and then allowed to survive for 21 days. For the rats, 6OHDA was injected into the midbrain and then allowed to survive for either 7, 28 or 84 days. Brains were processed for tyrosine hydroxylase (TH) and calbindin immunocytochemistry to label populations in the ventral and dorsal tiers of midbrain dopaminergic cells. In monkeys, while there was a decrease in the TH+ cell number in the ventral tier of MPTP-treated cases (65%), there was an overall increase (22%) in the TH+ and calbindin+ cell number in the dorsal tier. Double labelling studies indicate that approximately 50% of TH+ cells of the dorsal tier contain calbindin also. In rats, there was a decrease in TH+ cell number in the ventral tier of 6OHDA-lesioned cases (97%), and to a lesser extent, in the TH+ and calbindin+ cell number in the dorsal tier ( approximately 40%). In conclusion, we show a surprising increase in TH+ and calbindin+ cell number in the dorsal tier in response to MPTP insult; such an increase was not evident after 6OHDA insult. We suggest that the increase in antigen expression relates to the dopaminergic reinnervation of the striatum in MPTP-treated cases. We also suggest that the greater loss of dopaminergic cells in the ventral tier when compared to the dorsal tier relates to glutamate toxicity.
authors.affiliation: Department of Anatomy & Histology, University of Sydney, Australia.
authors.forename: Emily
authors.initials: E
authors.lastname: Fitzpatrick
authors.forename: Keyoumars
authors.initials: K
authors.lastname: Ashkan
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Wallace
authors.forename: Alim-Louis
authors.initials: AL
authors.lastname: Benabid
authors.forename: John
authors.initials: J
authors.lastname: Mitrofanis
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D002470:Cell Survival; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000633:toxicity; D000882:Haplorhini; D008251:Macaca; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects* / Q000473:pathology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009498:Neurotoxins / Q000494:pharmacology; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000032:analysis* / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
chemical_list: D018663:Adrenergic Agents; D015259:Dopamine Agents; D009498:Neurotoxins; D011954:Receptors, Dopamine; D016627:Oxidopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase