title: Selective expression of α-synuclein-immunoreactivity in vesicular acetylcholine transporter-immunoreactive axons in the guinea pig rectum and human colon.
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.
authors: Department of Human Physiology and Centre for Neuroscience, Flinders Medical Science and Technology, School of Medicine, Flinders University, Bedford Park, South Australia, Australia.
authors: Dale F
authors: DF
authors: Sharrad
authors: Elsbeth
authors: E
authors: de Vries
authors: Simon J H
authors: SJ
authors: Brookes
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000918:Antibody Specificity; D001369:Axons / Q000378:metabolism / Q000473:pathology; D059329:Cholinergic Neurons / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000294:innervation; D003248:Constipation / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007150:Immunohistochemistry / Q000592:standards; D016631:Lewy Bodies / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009197:Myenteric Plexus / Q000378:metabolism* / Q000473:pathology; D010300:Parkinson Disease / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D012007:Rectum / Q000294:innervation; D015203:Reproducibility of Results; D050494:Vesicular Acetylcholine Transport Proteins / Q000276:immunology / Q000378:metabolism*; D051844:alpha-Synuclein / Q000276:immunology / Q000378:metabolism*
chemical_list: C493459:SLC18A3 protein, human; C497604:SNCA protein, human; D050494:Vesicular Acetylcholine Transport Proteins; D051844:alpha-Synuclein