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Selective expression of α‐synuclein‐immunoreactivity in vesicular acetylcholine transporter‐immunoreactive axons in the guinea pig rectum and human colon
Author(s) -
Sharrad Dale F.,
de Vries Elsbeth,
Brookes Simon J.H.
Publication year - 2012
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.23198
Subject(s) - biology , vesicular acetylcholine transporter , guinea pig , acetylcholine , neuroscience , rectum , transporter , myenteric plexus , anatomy , immunohistochemistry , microbiology and biotechnology , endocrinology , medicine , immunology , biochemistry , gene , choline acetyltransferase
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. J. Comp. Neurol. 521:657–676, 2013. © 2012 Wiley Periodicals, Inc.