title: 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: 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 α-synuclein 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-α (CSPα), 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% ± 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% ± 1.3%, n = 4) compared with any of the other nine populations (P < 0.001). Among synaptophysin-, synaptotagmin-1-, synaptobrevin-2-, and CSPα-IR varicosities, 98% ± 0.7%, 96% ± 0.7%, 88% ± 1.6%, and 85% ± 2.9% (n = 4) contained α-synuclein immunoreactivity, respectively. Among α-synuclein-IR varicosities, 96% ± 0.9%, 99% ± 0.6%, 83% ± 1.9%, and 87% ± 2.3% (n = 4) contained synaptophysin-, synaptotagmin-1-, synaptobrevin-2-, and CSPα 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.
authors.affiliation: Department of Human Physiology and Centre for Neuroscience, Flinders Medical Science and Technology, School of Medicine, Flinders University, Bedford Park, South Australia 5042, Australia.
authors.forename: Dale F
authors.initials: DF
authors.lastname: Sharrad
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Gai
authors.forename: Simon J H
authors.initials: SJ
authors.lastname: Brookes
mesh_terms: D000368:Aged; D000818:Animals; D001369:Axons / Q000378:metabolism*; D015153:Blotting, Western; D017615:Enteric Nervous System / Q000166:cytology / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D050956:HSP40 Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D007082:Ileum / Q000294:innervation / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D009197:Myenteric Plexus / Q000166:cytology / Q000378:metabolism; D019579:Neocortex / Q000166:cytology / Q000378:metabolism; D016708:Synaptophysin / Q000096:biosynthesis*; D050863:Synaptotagmin I / Q000096:biosynthesis*; D050988:Vesicle-Associated Membrane Protein 2 / Q000096:biosynthesis*; D050494:Vesicular Acetylcholine Transport Proteins / Q000096:biosynthesis*; D051844:alpha-Synuclein / Q000096:biosynthesis*
chemical_list: D050956:HSP40 Heat-Shock Proteins; D008565:Membrane Proteins; D016708:Synaptophysin; D050863:Synaptotagmin I; D050988:Vesicle-Associated Membrane Protein 2; D050494:Vesicular Acetylcholine Transport Proteins; D051844:alpha-Synuclein; C088460:cysteine string protein