Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease

• Published in: The Journal of clinical investigation Vol. 120; no. 8; pp. 2745 - 2754
• Main Authors: Karachi, Carine, Grabli, David, Bernard, Frédéric A., Tandé, Dominique, Wattiez, Nicolas, Belaid, Hayat, Bardinet, Eric, Prigent, Annick, Nothacker, Hans-Peter, Hunot, Stéphane, Hartmann, Andreas, Lehéricy, Stéphane, Hirsch, Etienne C., François, Chantal
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.08.2010
• Subjects: Accidental Falls; Adult; Aged; Aged, 80 and over; Animals; Biomedical research; Brain; Female; Gait; Humans; Life Sciences; Macaca; Male; Mesencephalon; MPTP Poisoning; MPTP Poisoning - physiopathology; Neurons; Neurons and Cognition; Observations; Older people; Parasympathetic Nervous System; Parasympathetic Nervous System - physiology; Parkinson Disease; Parkinson Disease - physiopathology; Parkinson's disease; Pedunculopontine Tegmental Nucleus; Pedunculopontine Tegmental Nucleus - physiology; Physiological aspects; Postural Balance; Posture; Properties; France; United States
• ISSN: 0021-9738; 1558-8238; 1558-8238
• DOI: 10.1172/JCI42642

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.