Deletion of the vesicular acetylcholine transporter from pedunculopontine/laterodorsal tegmental neurons modifies gait. Issue 5 (6th January 2017)

• Record Type: Journal Article
• Authors: Janickova, Helena; Rosborough, Kaie; Al‐Onaizi, Mohammed; Kljakic, Ornela; Guzman, Monica S.; Gros, Robert; Prado, Marco A. M.; Prado, Vania F.
• Is Part Of: Journal of neurochemistry. Volume 140:Issue 5(2017)
• Page Start: 787
• Page End: 798
• Publication Date: 2017-01-06
• Subjects: acetylcholine -- balance -- gait -- motor disease -- Parkinson's disease -- pedunculopontine; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.13910
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract: Postural instability and gait disturbances, common disabilities in the elderly and frequently present in Parkinson's disease (PD), have been suggested to be related to dysfunctional cholinergic signaling in the brainstem. We investigated how long‐term loss of cholinergic signaling from mesopontine nuclei influence motor behaviors. We selectively eliminated the vesicular acetylcholine transporter (VAChT) in pedunculopontine and laterodorsal tegmental nuclei cholinergic neurons to generate mice with selective mesopontine cholinergic deficiency (VAChT E n1‐Cre‐flox/flox ). VAChT E n1‐Cre‐flox/flox mice did not show any gross health or neuromuscular abnormality on metabolic cages, wire‐hang and grip‐force tests. Young VAChT E n1‐Cre‐flox/flox mice (2–5 months‐old) presented motor learning/coordination deficits on the rotarod; moved slower, and had smaller steps on the catwalk, but showed no difference in locomotor activity on the open field. Old VAChT E n1‐Creflox/flox mice (13–16 months‐old) showed more pronounced motor learning/balance deficits on the rotarod, and more pronounced balance deficits on the catwalk. Furthermore, old mutants moved faster than controls, but with similar step length. Additionally, old VAChT‐deficient mice were hyperactive. These results suggest that dysfunction of cholinergic neurons from mesopontine nuclei, which is commonly seen in PD, has causal roles in motor functions. Prevention of mesopontine cholinergic failure may help to prevent/improve postural instability and falls in PD patients. Read the Editorial Highlight for this article onpage 688 . Abstract : Deficiency of pedunculopontine tegmental nucleus (PPT)/laterodorsal tegmental nucleus (LDT) cholinergic signaling disturbs coordination and gait in an age dependent way. These results support the hypothesis that long‐term degeneration of cholinergic neurons from PPT/LDT in Parkinson's disease and other parkinsonian disorders has a causal role to increase severity of motor symptoms. Read the Editorial Highlight for this article onpage 688 .