Selective coexpression of synaptic proteins, α‐synuclein, cysteine string protein‐α, synaptophysin, synaptotagmin‐1, and synaptobrevin‐2 in vesicular acetylcholine transporter‐immunoreactive axons in the guinea pig ileum

Abstract

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. Page 1

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“…Also, a decreasing density of asyn pathology in the myenteric plexus from the stomach to the transverse colon would suggest that the pathology was derived from DMV motor efferents, which are known to exhibit this pattern of innervation [7]. Of note, the majority of asyn-positive synapses in the rat myenteric plexus are DMV motor efferents, whereas sensory vagal afferents are asyn-negative and local enteric neurons express asyn at much lower frequencies [37, 46, 47, 54]. Thus, the DMV motor efferents could be a particular vulnerable system for asyn pathology and propagation.…”

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