Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease
Carine Karachi, David Grabli, Frédéric A. Bernard, Dominique Tandé, Nicolas Wattiez, Hayat Belaid, Eric Bardinet, Annick Prigent, Hans-Peter Nothacker, Stéphane Hunot, Andreas Hartmann, Stéphane Lehéricy, Etienne C. Hirsch, Chantal François
Carine Karachi, David Grabli, Frédéric A. Bernard, Dominique Tandé, Nicolas Wattiez, Hayat Belaid, Eric Bardinet, Annick Prigent, Hans-Peter Nothacker, Stéphane Hunot, Andreas Hartmann, Stéphane Lehéricy, Etienne C. Hirsch, Chantal François
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Research Article Neuroscience

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

Abstract

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.

Authors

Carine Karachi, David Grabli, Frédéric A. Bernard, Dominique Tandé, Nicolas Wattiez, Hayat Belaid, Eric Bardinet, Annick Prigent, Hans-Peter Nothacker, Stéphane Hunot, Andreas Hartmann, Stéphane Lehéricy, Etienne C. Hirsch, Chantal François

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Figure 3

Loss of PPN cholinergic neurons in MPTP-treated macaques.

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Loss of PPN cholinergic neurons in MPTP-treated macaques. (A) NADPH+ neu...
(A) NADPH+ neurons mapped in the PPN of a control brain of a young macaque; hatched areas denote myelinated nerve fibers in the brainstem and blue dots represent individual neurons. Low- and high-magnification images are shown at right. (B) Total number of NADPH+ neurons quantified in young and aged MPTP-intoxicated macaques compared with their respective controls (n = 4 per group). MPTP did not affect NADPH+ neurons in young animals, but induced a 30% loss of cholinergic neurons in aged monkeys. **P < 0.01, Mann-Whitney U test. Scale bars: 2 mm (map); 500 μm (low magnification); 100 μm (high magnification).