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Deletion of the vesicular acetylcholine transporter from pedunculopontine/laterodorsal tegmental neurons modifies gait.
- Source :
- Journal of Neurochemistry; Mar2017, Vol. 140 Issue 5, p787-798, 12p
- Publication Year :
- 2017
-
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 ( VACh T<superscript>E</superscript><superscript>n1-Cre-flox/flox</superscript>). VACh T<superscript>E</superscript><superscript>n1-Cre-flox/flox</superscript> mice did not show any gross health or neuromuscular abnormality on metabolic cages, wire-hang and grip-force tests. Young VACh T<superscript>E</superscript><superscript>n1-Cre-flox/flox</superscript> 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 VACh T<superscript>E</superscript><superscript>n1-Creflox/flox</superscript> 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00223042
- Volume :
- 140
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Journal of Neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 121268780
- Full Text :
- https://doi.org/10.1111/jnc.13910