TY - JOUR
T1 - Cell survival patterns in the pedunculopontine tegmental nucleus of methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkeys and 6OHDA-lesioned rats
T2 - Evidence for differences to idiopathic Parkinson disease patients?
AU - Heise, Claire E.
AU - Teo, Zui Chih
AU - Wallace, Bradley A.
AU - Ashkan, Keyoumars
AU - Benabid, Alim Louis
AU - Mitrofanis, John
PY - 2005/11
Y1 - 2005/11
N2 - We explore the patterns of cell loss in the pedunculopontine tegmental nucleus (PpT), a major locomotor and muscle tone suppression centre of the brainstem, in two animal models of Parkinson disease, namely MPTP (methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated monkeys and 6-hydroxydopamine(6OHDA)-lesioned rats. Although there have been many studies documenting the loss of dopaminergic cells from the substantia nigra in these animal models, there has been little, if any, documentation of a loss of cells in the PpT. Results were obtained from macaque monkeys (Macaca fascicularis) and Sprague-Dawley rats. For the monkey series, animals were injected intramuscularly with MPTP (0.2 mg/kg) for 8 days consecutively and then allowed to survive for 21 days thereafter. Each monkey underwent behavioural assessment for parkinsonian symptoms. For the rat series, 6OHDA was injected into the midbrain using stereotactic coordinates. Rats were then allowed to survive for either 7, 14, 28, or 84 days thereafter. Monkey and rat brains were aldehyde-fixed and processed for routine tyrosine hydroxylase (TH; to label nigral dopaminergic cells) and nitric oxide synthase (NOs; to label PpT cholinergic cells) immunocytochemistry. In monkeys, the morphology, distribution and number of NOs+ cells in the controls and MPTP-treated cases were very similar. In fact, in terms of number, there was only a 1% difference in the mean cell number between the controls and MPTP-treated cases. A comparable pattern was evident in 6OHDA-lesioned rats; there was no substantial difference in morphology, distribution and number of NOs+ cells on the 6OHDA-lesioned cases when compared to the controls at each of the survival periods post-surgery. In summary, we show no loss of the large cholinergic/NOs+ cells in the PpT in two animal models of Parkinson disease. This is in contrast to the heavy loss of these cells reported by previous findings in idiopathic Parkinson disease in patients.
AB - We explore the patterns of cell loss in the pedunculopontine tegmental nucleus (PpT), a major locomotor and muscle tone suppression centre of the brainstem, in two animal models of Parkinson disease, namely MPTP (methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated monkeys and 6-hydroxydopamine(6OHDA)-lesioned rats. Although there have been many studies documenting the loss of dopaminergic cells from the substantia nigra in these animal models, there has been little, if any, documentation of a loss of cells in the PpT. Results were obtained from macaque monkeys (Macaca fascicularis) and Sprague-Dawley rats. For the monkey series, animals were injected intramuscularly with MPTP (0.2 mg/kg) for 8 days consecutively and then allowed to survive for 21 days thereafter. Each monkey underwent behavioural assessment for parkinsonian symptoms. For the rat series, 6OHDA was injected into the midbrain using stereotactic coordinates. Rats were then allowed to survive for either 7, 14, 28, or 84 days thereafter. Monkey and rat brains were aldehyde-fixed and processed for routine tyrosine hydroxylase (TH; to label nigral dopaminergic cells) and nitric oxide synthase (NOs; to label PpT cholinergic cells) immunocytochemistry. In monkeys, the morphology, distribution and number of NOs+ cells in the controls and MPTP-treated cases were very similar. In fact, in terms of number, there was only a 1% difference in the mean cell number between the controls and MPTP-treated cases. A comparable pattern was evident in 6OHDA-lesioned rats; there was no substantial difference in morphology, distribution and number of NOs+ cells on the 6OHDA-lesioned cases when compared to the controls at each of the survival periods post-surgery. In summary, we show no loss of the large cholinergic/NOs+ cells in the PpT in two animal models of Parkinson disease. This is in contrast to the heavy loss of these cells reported by previous findings in idiopathic Parkinson disease in patients.
KW - 6-Hydroxydopamine
KW - Brainstem
KW - Cholinergic
KW - Dopaminergic
KW - Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
UR - http://www.scopus.com/inward/record.url?scp=28244501289&partnerID=8YFLogxK
U2 - 10.1007/s00429-005-0053-1
DO - 10.1007/s00429-005-0053-1
M3 - Article
SN - 0340-2061
VL - 210
SP - 287
EP - 302
JO - Anatomy and Embryology
JF - Anatomy and Embryology
IS - 4
ER -