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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ben R. Cairns ◽  
Benjamin Jevans ◽  
Atchariya Chanpong ◽  
Dale Moulding ◽  
Conor J. McCann
Keyword(s):  
Machine Learning ◽  
Nervous System ◽  
Enteric Nervous System ◽  
Structural Changes ◽  
Computational Analysis ◽  
Confocal Imaging ◽  
Learning Approaches ◽  
Composition And Structure ◽  
Oxide Synthase ◽  
Computational Image Analysis

AbstractNeuronal 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.

Inhibitory effect of melatonin on nitric oxide synthase in rat enteric nervous system

2001 ◽  
Vol 120 (5) ◽  
pp. A176-A176
Author(s):  
P KOPPITZ ◽  
M STORR ◽  
D SAUR ◽  
M KURJAK ◽  
H ALLESCHER
Keyword(s):  
Nitric Oxide ◽  
Nervous System ◽  
Nitric Oxide Synthase ◽  
Enteric Nervous System ◽  
Inhibitory Effect ◽  
Oxide Synthase

scholarly journals Transplantation of enteric nervous system stem cells rescues nitric oxide synthase deficient mouse colon

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Conor J. McCann ◽  
Julie E. Cooper ◽  
Dipa Natarajan ◽  
Benjamin Jevans ◽  
Laura E. Burnett ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Stem Cells ◽  
Nervous System ◽  
Nitric Oxide Synthase ◽  
Enteric Nervous System ◽  
Deficient Mouse ◽  
Mouse Colon ◽  
Oxide Synthase

Nitric oxide synthase immunoreactivity in the enteric nervous system of the developing human digestive tract

1994 ◽  
Vol 275 (2) ◽  
pp. 235-245 ◽  
Author(s):  
Jean-Pierre Timmermans ◽  
Martine Barbiers ◽  
Dietrich W. Scheuermann ◽  
Johannes J. Bogers ◽  
Dirk Adriaensen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nervous System ◽  
Nitric Oxide Synthase ◽  
Enteric Nervous System ◽  
Digestive Tract ◽  
Human Digestive Tract ◽  
Oxide Synthase

Inhibitory effect of melatonin on nitric oxide synthase in rat enteric nervous system

2001 ◽  
Vol 120 (5) ◽  
pp. A176
Author(s):  
Patrick B. Koppitz ◽  
Martin A. Storr ◽  
Dieter Saur ◽  
Manfred Kurjak ◽  
Hans-Dieter Allescher
Keyword(s):  
Nitric Oxide ◽  
Nervous System ◽  
Nitric Oxide Synthase ◽  
Enteric Nervous System ◽  
Inhibitory Effect ◽  
Oxide Synthase

scholarly journals Profiling immune cells in the kidney using tissue cytometry and machine learning

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0006802020
Author(s):  
Seth Winfree ◽  
Mohamad Al Hasan ◽  
Tarek M. El-Achkar
Keyword(s):  
Machine Learning ◽  
Immune System ◽  
Immune Cells ◽  
Quantitative Imaging ◽  
Kidney Tissue ◽  
Confocal Imaging ◽  
Qualitative Assessment ◽  
Multidimensional Data ◽  
Learning Approaches ◽  
Imaging Data

The immune system governs key functions that maintain renal homeostasis through various effector cells that reside in or infiltrate the kidney. These immune cells play an important role in shaping adaptive or maladaptive responses to local or systemic stress and injury. We increasingly recognize that microenvironments within the kidney are characterized by unique distribution of immune cells, the function of which depends on this unique spatial localization. Therefore, quantitative profiling of immune cells in intact kidney tissue becomes essential, particularly at a scale and resolution that allow the detection of differences between the various "nephro-ecosystems" in health and disease. In this review, we discuss advancements in tissue cytometry of the kidney, performed through multiplexed confocal imaging and analysis using the Volumetric tissue exploration and analysis (VTEA) software. We highlight how this tool has improved our understanding of the role of the immune system in the kidney and its relevance in pathobiology of renal disease. We also discuss how the field is increasingly incorporating machine learning to enhance the analytical potential of the imaging data and provide unbiased methods to explore and visualize multidimensional data. Such novel analytical methods could be particularly relevant when applied to profiling immune cells. Furthermore, machine learning approaches applied to cytometry could present venues for non-exhaustive exploration and classifications of cells from existing data and improving tissue economy. Therefore, tissue cytometry is transforming what used to be a qualitative assessment of the kidney into a highly quantitative imaging-based "omics" assessment that compliments other advanced molecular interrogation technologies.

scholarly journals Notable postnatal alterations in the myenteric plexus of normal human bowel

Gut ◽  
1999 ◽  
Vol 44 (5) ◽  
pp. 666-674 ◽  
Author(s):  
T Wester ◽  
D S O’Briain ◽  
P Puri
Keyword(s):  
Nitric Oxide ◽  
Nervous System ◽  
Nitric Oxide Synthase ◽  
Enteric Nervous System ◽  
Myenteric Plexus ◽  
Nadph Diaphorase ◽  
Intestinal Neuronal Dysplasia ◽  
Neuronal Marker ◽  
Normal Human ◽  
Oxide Synthase

BACKGROUNDNitric oxide is the most important transmitter in non-adrenergic non-cholinergic nerves in the human gastrointestinal tract. Impaired nitrergic innervation has been described in Hirschsprung’s disease, hypertrophic pyloric stenosis, and intestinal neuronal dysplasia (IND). Recent findings indicate that hyperganglionosis, one of the major criteria of IND, is age dependent. However, information is scanty regarding the neurone density in normal human bowel in the paediatric age group.AIMSTo determine neurone density, morphology, and nitric oxide synthase distribution of the normal myenteric plexus at different ages during infancy and childhood.METHODSSpecimens were obtained from small bowel and colon in 20 children, aged one day to 15 years, at postmortem examination. Whole mount preparations were made of the myenteric plexus, which were subsequently stained using NADPH diaphorase histochemistry (identical to nitric oxide synthase) and cuprolinic blue (a general neuronal marker). The morphology of the myenteric plexus was described and the neurone density estimated.RESULTSThe myenteric plexus meshwork becomes less dense during the first years of life. The density of ganglion cells in the myenteric plexus decreases significantly with age during the first three to four years of life. The NADPH diaphorase positive (nitrergic) subpopulation represents about 34% of all neurones in the myenteric plexus.CONCLUSIONSThe notable decrease in neurone density in the myenteric plexus during the first years of life indicates that development is still an ongoing process in the postnatal enteric nervous system. Applied to the clinical situation, this implies that interpretation of enteric nervous system pathology is dependent on the age of the patient.

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