Selective expression of α-synuclein-immunoreactivity in vesicular acetylcholine transporter-immunoreactive axons in the guinea-pig rectum and human colon

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dc.contributor.author Sharrad, DF
dc.contributor.author de Vries, E
dc.contributor.author Brookes, Simon Jonathan
dc.date.accessioned 2013-08-26T04:52:34Z
dc.date.available 2013-08-26T04:52:34Z
dc.date.issued 17/12/2012
dc.description This article appeared in a journal published by Wiley-Blackwell. Under Wiley's copyright, mandated authors are not permitted to make work available in an institutional repository. en
dc.description.abstract Parkinson's disease is a neurodegenerative disorder characterized by motor and nonmotor impairments, including constipation. The hallmark pathological features of Parkinson's disease are Lewy bodies and neurites, of which aggregated α-synuclein is a major constituent. Frequently, Lewy pathology is identified in the distal gut of constipated Parkinson's disease patients. The neurons that innervate the distal gut that express α-synuclein have not been identified. We used multiple-labeling immunohistochemistry and anterograde tracing to quantify which neurons projecting to the guinea pig rectum and human colon expressed α-synuclein in their axons. α-Synuclein-immunoreactivity was present in 24 ± 0.7% of somatostatin (SOM)-immunoreactive (IR) varicosities; 20 ± 4.3% of substance P (SP)-IR varicosities and 9 ± 1.3% vasoactive intestinal polypeptide (VIP)-IR varicosities in guinea pig rectal myenteric ganglia. However, α-synuclein-immunoreactivity was localized in significantly more vesicular acetylcholine transporter (VAChT)-IR varicosities (88 ± 3%, P < 0.001). Of SOM-IR, SP-IR, and VIP-IR varicosities that lacked VAChT-immunoreactivity, only 1 ± 0.3%, 0 ± 0.3%, and 0% contained α-synuclein-immunoreactivity, respectively. 71 ± 0.8% of VAChT-IR varicosities in myenteric ganglia of human colon were α-synuclein-IR. In guinea pig rectal myenteric ganglia, α-synuclein- and VAChT-immunoreactivity coexisted in 15 ± 1.4% of biotinamide-labeled extrinsic varicosities; only 1 ± 0.3% of biotinamide-labeled extrinsic varicosities contained α-synuclein-immunoreactivity without VAChT-immunoreactivity. α-Synuclein expression in axons to the distal gut correlates closely with expression of the cholinergic marker, VAChT. This is the first report of cell-selective α-synuclein expression in the nervous system. Our results suggest cholinergic neurons in the gut may be vulnerable in Parkinson's disease. en
dc.description.sponsorship Australian National Health & Medical Research Council en
dc.identifier.citation Sharrad DF, De Vries E, Brookes SJH (2013). Selective expression of α-synuclein-immunoreactivity in vesicular acetylcholine transporter-immunoreactive axons in the guinea-pig rectum and human colon.  Journal of Comparative Neurology, 521(3), 657-676. en
dc.identifier.doi https://doi.org/10.1002/cne.23198 en
dc.identifier.issn 0021-9967
dc.identifier.uri http://hdl.handle.net/2328/26992
dc.language.iso en en_US
dc.publisher Wiley-Blackwell en_US
dc.relation http://purl.org/au-research/grants/nhmrc/595969
dc.relation.grantnumber NHMRC/595969
dc.rights Copyright 2012 Wiley Periodicals, Inc.
dc.rights.holder Wiley-Blackwell
dc.subject Parkinson's disease
dc.subject Lewy pathology
dc.subject Cholinergic neurons
dc.title Selective expression of α-synuclein-immunoreactivity in vesicular acetylcholine transporter-immunoreactive axons in the guinea-pig rectum and human colon en_US
dc.type Article en
local.contributor.authorOrcidLookup Brookes, Simon Jonathan: https://orcid.org/0000-0001-5635-0876 en_US
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