title: Alpha-synuclein immunopositive aggregates in the myenteric plexus of the aging Fischer 344 rat.
abstract: Dystrophic axons and terminals are common in the myenteric plexus and smooth muscle of the gastrointestinal (GI) tract of aged rats. In young adult rats, alpha-synuclein in its normal state is abundant throughout the myenteric plexus, making this protein-which is prone to fibrillization-a candidate marker for axonopathies in the aged rat. To determine if aggregation of alpha-synuclein is involved in the formation of age-related enteric neuropathies, we sampled the stomach, small intestine and large intestine of adult, middle-aged, and aged virgin male Fischer 344 rats stained for alpha-synuclein in both its normal and pathological states. Alpha-synuclein-positive dystrophic axons and terminals were present throughout the GI tract of middle-aged and aged rats, with immunohistochemical double labeling demonstrating co-localization within nitric oxide synthase-, calretinin-, calbindin-, or tyrosine hydroxylase-positive markedly swollen neurites. However, other dystrophic neurites positive for each of these four markers were not co-reactive for alpha-synuclein. Similarly, a subpopulation of alpha-synuclein inclusions contained deposits immunostained with an anti-tau phospho-specific Ser(262) antibody, but not all of these hyperphosphorylated tau-positive aggregates were co-localized with alpha-synuclein. The presence of heteroplastic and potentially degenerating neural elements and protein aggregates both positive and negative for alpha-synuclein suggests a complex chronological relationship between the onset of degenerative changes and the accumulation of misfolded proteins. Additionally, proteins other than alpha-synuclein appear to be involved in age-related axonopathies. Finally, this study establishes the utility of the aging Fischer 344 rat for the study of synucleopathies and tauopathies in the GI tract.
authors: Purdue University, Department of Psychological Sciences, 703 Third Street, West Lafayette, IN 47907-2081, USA. rphillip@psych.purdue.edu
authors: Robert J
authors: RJ
authors: Phillips
authors: Gary C
authors: GC
authors: Walter
authors: Brittany E
authors: BE
authors: Ringer
authors: Katherine M
authors: KM
authors: Higgs
authors: Terry L
authors: TL
authors: Powley
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000473:pathology* / Q000503:physiopathology; D001369:Axons / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000294:innervation / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000378:metabolism / Q000473:pathology; D008297:Male; D009197:Myenteric Plexus / Q000378:metabolism* / Q000473:pathology*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D017510:Protein Folding; D051381:Rats; D011916:Rats, Inbred F344; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014855:Wallerian Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051844:alpha-Synuclein / Q000032:analysis / Q000378:metabolism*; D016875:tau Proteins / Q000032:analysis / Q000378:metabolism
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; D051844:alpha-Synuclein; D016875:tau Proteins; D052248:Nitric Oxide Synthase Type I; D014446:Tyrosine 3-Monooxygenase