Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease.
Gait disorders and postural instability, which are commonly observed in elderly patients with Parkinson disease (PD), respond poorly to dopaminergic agents used to treat other parkinsonian symptoms. The brain structures underlying gait disorders and falls in PD and aging remain to be characterized. Using functional MRI in healthy human subjects, we have shown here that activity of the mesencephalic locomotor region (MLR), which is composed of the pedunculopontine nucleus (PPN) and the adjacent cuneiform nucleus, was modulated by the speed of imagined gait, with faster imagined gait activating a discrete cluster within the MLR. Furthermore, the presence of gait disorders in patients with PD and in aged monkeys rendered parkinsonian by MPTP intoxication correlated with loss of PPN cholinergic neurons. Bilateral lesioning of the cholinergic part of the PPN induced gait and postural deficits in nondopaminergic lesioned monkeys. Our data therefore reveal that the cholinergic neurons of the PPN play a central role in controlling gait and posture and represent a possible target for pharmacological treatment of gait disorders in PD.
Karachi
Carine
C
Université Pierre et Marie Curie -Paris 6, CR-ICM, UMR-S975, Paris, France.
Grabli
David
D
Bernard
Frédéric A
FA
Tandé
Dominique
D
Wattiez
Nicolas
N
Belaid
Hayat
H
Bardinet
Eric
E
Prigent
Annick
A
Nothacker
Hans-Peter
HP
Hunot
Stéphane
S
Hartmann
Andreas
A
Lehéricy
Stéphane
S
Hirsch
Etienne C
EC
François
Chantal
C
D000058:Accidental Falls; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D005260:Female; D005684:Gait; D006801:Humans; D020267:MPTP Poisoning / Q000503:physiopathology; D008251:Macaca; D008297:Male; D010275:Parasympathetic Nervous System / Q000502:physiology*; D010300:Parkinson Disease / Q000503:physiopathology*; D045042:Pedunculopontine Tegmental Nucleus / Q000502:physiology*; D004856:Postural Balance