BACKGROUND: This experiment assessed normative expression patterns of alpha-synuclein (SYNC), including ganglionic remodeling and development of SYNC pathologies, in the submucosal plexus (SMP) of the colon during healthy aging. The observations address age-associated changes in bowel function and are relevant to evaluations of SMP-containing colonic biopsies for SYNC or synucleinopathies associated with aging and peripheral neurodegenerative diseases. METHODS: Colonic submucosal whole mounts from groups of virgin male Fischer 344 rats (n ≥ 8 per group) at 4, 8, 16, and 24 months of age were processed immunohistochemically for SYNC and the pan-neuronal marker HuC/D. In addition, macrophages immunoreactive for MHCII were examined. Stereological protocols were used to generate unbiased estimates of neuron density, neurons per ganglion, neurons per ganglionic area, and neuron size. KEY RESULTS: The protein SYNC was expressed in a subpopulation of SMP neurons, in both nucleus and cytoplasm. The general age-associated pattern across different cell counts was an increase in the number of SYNC+ neurons between 4 and 8 months of age, with progressively decreasing numbers of both SYNC+ and SYNC- neurons over the remaining lifespan. The soma size of SYNC+ neurons increased progressively with age. Aggregated SYNC occurred in the aging SMP, and macrophages with alternatively activated profiles were located adjacent to pathological SYNC deposits, consistent with ongoing phagocytosis. CONCLUSIONS & INFERENCES: Changes in SYNC expression with age, including a baseline of accumulating synucleinopathies in the healthy aging SMP, need to be considered when interpreting either functional disturbances or biopsies of the aging colon.
BACKGROUND: This experiment assessed normative expression patterns of alpha-synuclein (SYNC), including ganglionic remodeling and development of SYNC pathologies, in the submucosal plexus (SMP) of the colon during healthy aging. The observations address age-associated changes in bowel function and are relevant to evaluations of SMP-containing colonic biopsies for SYNC or synucleinopathies associated with aging and peripheral neurodegenerative diseases. METHODS:Colonic submucosal whole mounts from groups of virgin male Fischer 344 rats (n ≥ 8 per group) at 4, 8, 16, and 24 months of age were processed immunohistochemically for SYNC and the pan-neuronal marker HuC/D. In addition, macrophages immunoreactive for MHCII were examined. Stereological protocols were used to generate unbiased estimates of neuron density, neurons per ganglion, neurons per ganglionic area, and neuron size. KEY RESULTS: The protein SYNC was expressed in a subpopulation of SMP neurons, in both nucleus and cytoplasm. The general age-associated pattern across different cell counts was an increase in the number of SYNC+ neurons between 4 and 8 months of age, with progressively decreasing numbers of both SYNC+ and SYNC- neurons over the remaining lifespan. The soma size of SYNC+ neurons increased progressively with age. Aggregated SYNC occurred in the aging SMP, and macrophages with alternatively activated profiles were located adjacent to pathological SYNC deposits, consistent with ongoing phagocytosis. CONCLUSIONS & INFERENCES: Changes in SYNC expression with age, including a baseline of accumulating synucleinopathies in the healthy aging SMP, need to be considered when interpreting either functional disturbances or biopsies of the aging colon.
Authors: Heiko Braak; Magdalena Sastre; Jürgen R E Bohl; Rob A I de Vos; Kelly Del Tredici Journal: Acta Neuropathol Date: 2007-02-09 Impact factor: 17.088
Authors: Fredric P Manfredsson; Kelvin C Luk; Matthew J Benskey; Aysegul Gezer; Joanna Garcia; Nathan C Kuhn; Ivette M Sandoval; Joseph R Patterson; Alana O'Mara; Reid Yonkers; Jeffrey H Kordower Journal: Neurobiol Dis Date: 2018-01-16 Impact factor: 5.996