Automated computational analysis reveals structural changes in the enteric nervous system of nNOS deficient mice

Abstract Neuronal nitric oxide synthase (nNOS) neurons play a fundamental role in inhibitory neurotransmission, within the enteric nervous system (ENS), and in the establishment of gut motility patterns. Clinically, loss or disruption of nNOS neurons has been shown in a range of enteric neuropathies...

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Autores principales:	Ben R. Cairns, Benjamin Jevans, Atchariya Chanpong, Dale Moulding, Conor J. McCann
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d058b11d002948a896fc02e04aee5f40
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spelling	oai:doaj.org-article:d058b11d002948a896fc02e04aee5f402021-12-02T18:53:14ZAutomated computational analysis reveals structural changes in the enteric nervous system of nNOS deficient mice10.1038/s41598-021-96677-x2045-2322https://doaj.org/article/d058b11d002948a896fc02e04aee5f402021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96677-xhttps://doaj.org/toc/2045-2322Abstract Neuronal nitric oxide synthase (nNOS) neurons play a fundamental role in inhibitory neurotransmission, within the enteric nervous system (ENS), and in the establishment of gut motility patterns. Clinically, loss or disruption of nNOS neurons has been shown in a range of enteric neuropathies. However, the effects of nNOS loss on the composition and structure of the ENS remain poorly understood. The aim of this study was to assess the structural and transcriptional consequences of loss of nNOS neurons within the murine ENS. Expression analysis demonstrated compensatory transcriptional upregulation of pan neuronal and inhibitory neuronal subtype targets within the Nos1 −/− colon, compared to control C57BL/6J mice. Conventional confocal imaging; combined with novel machine learning approaches, and automated computational analysis, revealed increased interconnectivity within the Nos1 −/− ENS, compared to age-matched control mice, with increases in network density, neural projections and neuronal branching. These findings provide the first direct evidence of structural and molecular remodelling of the ENS, upon loss of nNOS signalling. Further, we demonstrate the utility of machine learning approaches, and automated computational image analysis, in revealing previously undetected; yet potentially clinically relevant, changes in ENS structure which could provide improved understanding of pathological mechanisms across a host of enteric neuropathies.Ben R. CairnsBenjamin JevansAtchariya ChanpongDale MouldingConor J. McCannNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ben R. Cairns Benjamin Jevans Atchariya Chanpong Dale Moulding Conor J. McCann Automated computational analysis reveals structural changes in the enteric nervous system of nNOS deficient mice
description	Abstract Neuronal nitric oxide synthase (nNOS) neurons play a fundamental role in inhibitory neurotransmission, within the enteric nervous system (ENS), and in the establishment of gut motility patterns. Clinically, loss or disruption of nNOS neurons has been shown in a range of enteric neuropathies. However, the effects of nNOS loss on the composition and structure of the ENS remain poorly understood. The aim of this study was to assess the structural and transcriptional consequences of loss of nNOS neurons within the murine ENS. Expression analysis demonstrated compensatory transcriptional upregulation of pan neuronal and inhibitory neuronal subtype targets within the Nos1 −/− colon, compared to control C57BL/6J mice. Conventional confocal imaging; combined with novel machine learning approaches, and automated computational analysis, revealed increased interconnectivity within the Nos1 −/− ENS, compared to age-matched control mice, with increases in network density, neural projections and neuronal branching. These findings provide the first direct evidence of structural and molecular remodelling of the ENS, upon loss of nNOS signalling. Further, we demonstrate the utility of machine learning approaches, and automated computational image analysis, in revealing previously undetected; yet potentially clinically relevant, changes in ENS structure which could provide improved understanding of pathological mechanisms across a host of enteric neuropathies.
format	article
author	Ben R. Cairns Benjamin Jevans Atchariya Chanpong Dale Moulding Conor J. McCann
author_facet	Ben R. Cairns Benjamin Jevans Atchariya Chanpong Dale Moulding Conor J. McCann
author_sort	Ben R. Cairns
title	Automated computational analysis reveals structural changes in the enteric nervous system of nNOS deficient mice
title_short	Automated computational analysis reveals structural changes in the enteric nervous system of nNOS deficient mice
title_full	Automated computational analysis reveals structural changes in the enteric nervous system of nNOS deficient mice
title_fullStr	Automated computational analysis reveals structural changes in the enteric nervous system of nNOS deficient mice
title_full_unstemmed	Automated computational analysis reveals structural changes in the enteric nervous system of nNOS deficient mice
title_sort	automated computational analysis reveals structural changes in the enteric nervous system of nnos deficient mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d058b11d002948a896fc02e04aee5f40
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Automated computational analysis reveals structural changes in the enteric nervous system of nNOS deficient mice

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