This is the peer reviewed version of the following article:Sharrad DF, Gai WP, Brookes SJ. Selective coexpression of synaptic proteins, α-synuclein, cysteine string protein-α, synaptophysin, synaptotagmin-1, and synaptobrevin-2 in vesicular acetylcholine transporterimmunoreactive axons in the guinea pig ileum. J Comp Neurol. 2013 Aug 1;521(11):2523-37.which has been published in final form at doi:10.1002/cne.23296.This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for SelfArchiving. Keywords synaptic transmission; neurodegeneration; Parkinson's disease; enteric nervous system ABSTRACT Parkinson's disease is a neurodegenerative disorder characterized by Lewy bodies and neurites composed mainly of the presynaptic protein α-Synuclein. Frequently, Lewy bodies and neurites are identified in the gut of Parkinson's disease patients and may underlie associated gastrointestinal dysfunctions. We recently reported selective expression of α-Synuclein in the axons of cholinergic neurons in the guinea pig and human distal gut; however, it is not clear whether asynuclein expression varies along the gut, nor how closely expression is associated with other synaptic proteins. We used multiple-labeling immunohistochemistry to quantify which neurons in the guinea pig ileum expressed α-Synuclein, cysteine string protein-a (CSPa), synaptophysin, synaptotagmin-1, or synaptobrevin-2 in their axons. Among the 10 neurochemically defined axonal populations, a significantly greater proportion of vesicular acetylcholine transporter-immunoreactive (VAChT-IR) varicosities (80% 6 1.7%, n . 4, P < 0.001) contained α-Synuclein immunoreactivity, and a significantly greater proportion of α-Synuclein-IR axons also contained VAChT immunoreactivity (78% 6 1.3%, n . 4) compared with any of the other nine populations (P < 0.001). Among synaptophysin-, synaptotagmin-1-, synaptobrevin-2-, and CSPa-IR varicosities, 98% 6 0.7%, 96% 6 0.7%, 88% 6 1.6%, and 85% 6 2.9% (n . 4) contained α-Synuclein immunoreactivity, respectively. Among α-Synuclein-IR varicosities, 96% 6 0.9%, 99% 6 0.6%, 83% 6 1.9%, and 87% 6 2.3% (n . 4) contained synaptophysin-, synaptotagmin-1-, synaptobrevin-2-, and CSPa immunoreactivity, respectively. We report a close association between the expression of α-Synuclein and the expression of other synaptic proteins in cholinergic axons in the guinea pig ileum. Selective expression of α-Synuclein may relate to the neurotransmitter system utilized and predispose cholinergic enteric neurons to degeneration in Parkinson's disease.
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