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dc.contributor.authorKeating, Christopher
dc.contributor.authorNochi, Linda
dc.contributor.authorYu, Yang
dc.contributor.authorDonovan, Jemma
dc.contributor.authorGrundy, D
dc.date.accessioned2016-11-11T15:59:04Z
dc.date.available2016-11-11T15:59:04Z
dc.date.issued2016-08-14
dc.identifier.citationKeating , C , Nochi , L , Yu , Y , Donovan , J & Grundy , D 2016 , ' Ageing and gastrointestinal sensory function: altered colonic mechanosensory and chemosensory function in the aged mouse. ' , Journal of Physiology , vol. 594 , no. 16 , pp. 4549- 64 . https://doi.org/10.1113/JP271403
dc.identifier.issn0022-3751
dc.identifier.urihttp://hdl.handle.net/2299/17312
dc.description.abstractAgeing has a profound effect upon gastrointestinal function through mechanisms that are poorly understood. Here we investigated the effect of age upon gastrointestinal sensory signalling pathways in order to address the mechanisms underlying these changes. In vitro mouse colonic and jejunal preparations with attached splanchnic and mesenteric nerves were used to study mechanosensory and chemosensory afferent function in 3-, 12- and 24-month-old C57BL/6 animals. Quantitative RT-PCR was used to investigate mRNA expression in colonic tissue and dorsal root ganglion (DRG) cells isolated from 3- and 24-month animals, and immunohistochemistry was used to quantify the number of 5-HT-expressing enterochromaffin (EC) cells. Colonic and jejunal afferent mechanosensory function was attenuated with age and these effects appeared earlier in the colon compared to the jejunum. Colonic age-related loss of mechanosensory function was more pronounced in high-threshold afferents compared to low-threshold afferents. Chemosensory function was attenuated in the 24-month colon, affecting TRPV1 and serotonergic signalling pathways. High-threshold mechanosensory afferent fibres and small-diameter DRG neurons possessed lower functional TRPV1 receptor responses, which occurred without a change in TRPV1 mRNA expression. Serotonergic signalling was attenuated at 24 months, but TPH1 and TPH2 mRNA expression was elevated in colonic tissue. In conclusion, we saw an age-associated decrease in afferent mechanosensitivity in the mouse colon affecting HT units. These units have the capacity to sensitise in response to injurious events, and their loss in ageing may predispose the elderly to lower awareness of GI injury or disease.en
dc.format.extent955028
dc.language.isoeng
dc.relation.ispartofJournal of Physiology
dc.titleAgeing and gastrointestinal sensory function: altered colonic mechanosensory and chemosensory function in the aged mouse.en
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionCentre for Research in Mechanisms of Disease and Drug Discovery
dc.contributor.institutionDepartment of Clinical, Pharmaceutical and Biological Science
dc.contributor.institutionBasic and Clinical Science Unit
dc.contributor.institutionCentre for Health Services and Clinical Research
dc.description.statusPeer reviewed
rioxxterms.versionofrecord10.1113/JP271403
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue


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