Dopaminergic cells in the periaqueductal grey matter of MPTP-treated monkeys and mice; patterns of survival and effect of deep brain stimulation and lesion of the subthalamic nucleus.
In this anatomical study, we have examined the number of tyrosine hydroxylase (TH) cells in the periaqueductal grey matter (PAG) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys and mice; further, we explored whether kainic acid lesion or deep brain stimulation (DBS) of the subthalamic nucleus (STN) in MPTP-treated monkeys has any impact on the number of TH(+) cells in the PAG. For monkeys, there were four groups: Normal, MPTP, STN-lesioned (+MPTP) and STN-DBS (+MPTP). For mice, BALB/c albino mice were divided into three groups, Saline, MPTP_50 (50 mg/kg), MPTP_100 (100 mg/kg). Animals were perfused transcardially with aldehyde fixative 6-12 days after their last MPTP injection. Brains were processed for immunochemistry and the number of cells was estimated using the optical fractionator method. Our results revealed significant reductions (25-30%) in TH(+) cell number in the PAG of MPTP-treated monkeys and mice compared to controls. These reductions were not as substantial as those recorded in the SNc in the same animals (40-60%). Further, in monkeys, there were significantly more TH(+) cells in the PAG of STN-lesioned and STN-DBS groups compared to the MPTP group. In fact, the number of TH(+) cells in the STN alteration cases were similar to the Normal group. In summary, our results indicated that MPTP is toxic to TH(+) cells in the PAG of monkeys and mice and that in monkeys, lesion or DBS of the STN offers neuroprotection against this toxicity.
Discipline of Anatomy & Histology F13, Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia.
Victoria E
VE
Shaw
Kevin A
KA
Keay
Keyoumars
K
Ashkan
Alim-Louis
AL
Benabid
John
J
Mitrofanis
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D002452:Cell Count / Q000379:methods; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D046690:Deep Brain Stimulation / Q000009:adverse effects*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000633:toxicity; D020267:MPTP Poisoning / Q000473:pathology* / Q000628:therapy; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D010487:Periaqueductal Gray / Q000473:pathology*; D020531:Subthalamic Nucleus / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015259:Dopamine Agents; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine