Evidence for a dopaminergic innervation of the pedunculopontine nucleus in monkeys, and its drastic reduction after MPTP intoxication.
The involvement of the pedunculopontine nucleus (PPN) and the adjacent cuneiform nucleus (CuN), known as the mesencephalic locomotor area, in the pathophysiology of parkinsonian symptoms is receiving increasing attention. Taking into account the role of dopamine (DA) in motor control and its degeneration in Parkinson's disease, this neurotransmitter could induce dysfunction in the PPN and CuN through a direct dopaminergic innervation of these brainstem structures. This study provides the first demonstration that the PPN and CuN are innervated by dopamine transporter-bearing fibres in normal monkeys, which points to a novel dopaminergic system that targets the lower brainstem. Intoxication with MPTP induced a significant loss of dopamine transporter-positive fibres in the PPN and CuN of young (3-5 years old) acutely or chronically intoxicated monkeys compared with control animals. The more severe DA depletion found after chronic intoxication may explain, at least in part, deficits that appear late in the evolution of Parkinson's disease. A drastic loss of DA fibres was also observed in aged acutely intoxicated monkeys (about 30 years old) suggesting that age- and disease-related loss of dopaminergic fibres might be responsible for symptoms, such as gait disorders, that are more severe in elderly parkinsonian patients.
Rolland
Anne-Sophie
AS
INSERM, UMR_S975, Experimental Therapeutics of Neurodegeneration, Paris, France.
Tandé
Dominique
D
Herrero
Maria-Trinidad
MT
Luquin
Maria-Rosario
MR
Vazquez-Claverie
Marianne
M
Karachi
Carine
C
Hirsch
Etienne C
EC
François
Chantal
C
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D000109:Acetylcholine / Q000378:metabolism; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000032:analysis / Q000378:metabolism; D007150:Immunohistochemistry; D008251:Macaca; D026901:Membrane Transport Proteins / Q000032:analysis / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009498:Neurotoxins / Q000009:adverse effects; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D045042:Pedunculopontine Tegmental Nucleus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D026901:Membrane Transport Proteins; D009498:Neurotoxins; C065637:choline transporter; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D000109:Acetylcholine; D004298:Dopamine