Alpha-synuclein immunopositive aggregates in the myenteric plexus of the aging Fischer 344 rat

作者：Phillips Robert J^*; Walter Gary C; Ringer Brittany E; Higgs Katherine M; Powley Terry L

来源：Experimental Neurology, 2009, 220(1): 109-119.

DOI：10.1016/j.expneurol.2009.07.025

• Calbindin
• Calcitonin gene-related peptide
• Calretinin
• Enteric nervous system
• Lewy neurites/bodies
• Nitric oxide synthase
• Parkinson's disease
• Tau
• Tyrosine hydroxylase

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 market 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.

• 出版日期2009-11