Sympathetic Pathways Target Cholinergic Neurons in the Human Colonic Myenteric Plexus

Parker, D R; Wiklendt, Lukasz; Humenick, Adam; Chen, Bao Nan; Sia, Tiong Cheng; Wattchow, David; Dinning, Phil G.; Brookes, Simon J.

doi:10.3389/fnins.2022.863662

Cited by 9 publications

(8 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, the majority of postganglionic catecholaminergic axons (Figure 7) appeared to pass through ICG rather than directly interact with their PNs (Figure 9a1,a2). This sharply contrasted with the catecholaminergic nerve innervation of the gastrointestinal tract where TH‐IR axons make numerous synaptic‐like varicose endings around many myenteric ganglionic neurons in the stomach and small intestine (Figure 9b,c, arrowheads), which is consistent with previous reports (Hibberd et al., 2020; Parker et al., 2022; Powley et al., 2016).…”

Section: Resultssupporting

confidence: 91%

Catecholaminergic axon innervation and morphology in flat‐mounts of atria and ventricles of mice

Bizanti

Zhang

Harden

et al. 2023

J of Comparative Neurology

View full text Add to dashboard Cite

Sympathetic efferent axons regulate cardiac functions. However, the topographical distribution and morphology of cardiac sympathetic efferent axons remain insufficiently characterized due to the technical challenges involved in immunohistochemical labeling of the thick walls of the whole heart. In this study, flat-mounts of the left and right atria and ventricles of FVB mice were immunolabeled for tyrosine hydroxylase (TH), a marker of sympathetic nerves. Atrial and ventricular flat-mounts were scanned using a confocal microscope to construct montages. We found (1) In the atria: A few large TH-immunoreactive (IR) axon bundles entered both atria, branched into small bundles and then single axons that eventually formed very dense terminal networks in the epicardium, myocardium and inlet regions of great vessels to the atria. Varicose TH-IR axons formed close contact with cardiomyocytes, vessels, and adipocytes.Multiple intrinsic cardiac ganglia (ICG) were identified in the epicardium of both atria, and a subpopulation of the neurons in the ICG were TH-IR. Most TH-IR axons in bundles traveled through ICG before forming dense varicose terminal networks in cardiomyocytes. We did not observe varicose TH-IR terminals encircling ICG neurons. (2) In the left and right ventricles and interventricular septum: TH-IR axons formed dense terminal networks in the epicardium, myocardium, and vasculature. Collectively, TH labeling is achievable in flat-mounts of thick cardiac walls, enabling detailed mapping of catecholaminergic axons and terminal structures in the whole heart at single-cell/axon/varicosity scale. This approach provides a foundation for future quantification of the topographical organization of the cardiac sympathetic innervation in different pathological conditions.

show abstract

Section: Resultssupporting

confidence: 91%

Catecholaminergic axon innervation and morphology in flat‐mounts of atria and ventricles of mice

Bizanti

Zhang

Harden

et al. 2023

J of Comparative Neurology

View full text Add to dashboard Cite

show abstract

“…As previously described ( Parker et al, 2022 ), the full circumference preparations underwent elution to remove bound primary and secondary antisera, allowing a new layer of different markers of interest to be applied. In brief, preparations were submerged in a 2-mercaptoethanol/SDS buffer (2-ME/SDS) ( Gendusa et al, 2014 ) and incubated in a pre-heated water bath (56°C) for 1 h with agitation at 60 rpm.…”

Section: Methodsmentioning

confidence: 99%

Characterisation of parasympathetic ascending nerves in human colon

et al. 2022

Self Cite

View full text Add to dashboard Cite

BackgroundIn the human large bowel, sacral parasympathetic nerves arise from S2 to S4, project to the pelvic plexus (“hypogastric plexus”) and have post-ganglionic axons entering the large bowel near the rectosigmoid junction. They then run long distances orally or aborally within the bowel wall forming “ascending nerves” or “shunt fascicles” running in the plane of the myenteric plexus. They form bundles of nerve fibres that can be distinguished from the myenteric plexus by their straight orientation, tendency not to merge with myenteric ganglia and greater width.AimTo identify reliable marker(s) to distinguish these bundles of ascending nerves from other extrinsic and intrinsic nerves in human colon.MethodsHuman colonic segments were obtained with informed consent, from adult patients undergoing elective surgery (n = 21). Multi-layer immunohistochemical labelling with neurofilament-H (NF200), myelin basic protein (MBP), von Willebrand factor (vWF), and glucose transporter 1 (GLUT1), and rapid anterograde tracing with biotinamide, were used to compare ascending nerves and lumbar colonic nerves.ResultsThe rectosigmoid and rectal specimens had 6–11 ascending nerves spaced around their circumference. Distal colon specimens typically had 1–3 ascending nerves, with one located near the mesenteric taenia coli. No ascending nerves were observed in ascending colon specimens. GLUT1 antisera labelled both sympathetic lumbar colonic nerves and ascending nerves in the gut wall. Lumbar colonic nerves joined the myenteric plexus and quickly lost GLUT1 labelling, whereas GLUT1 staining labelled parasympathetic ascending nerves over many centimetres.ConclusionAscending nerves can be distinguished in the colorectum of humans using GLUT1 labelling combined with NF200.

show abstract

“…Noradrenaline inhibits intestinal motility through inhibition of acetylcholine release (Scheibner et al, 2002;Stebbing et al, 2001). This is supported by immunohistochemical findings in humans which suggest that sympathetic noradrenergic fibres preferentially target excitatory cholinergic neurons in the myenteric plexus to modulate intestinal motility (Parker et al, 2022). However, in the mouse, individual sympathetic fibres do not appear to innervate the entire GI tract equally, but instead project to distinct areas in the colon and modulate the activity of myenteric neurons in the proximal and distal colon independently.…”

Section: Effects Of Acute Stress On Gastrointestinal Physiology and F...mentioning

confidence: 90%

The impact of acute and chronic stress on gastrointestinal physiology and function: a microbiota–gut–brain axis perspective

Leigh,

Uhlig,

Wilmes

et al. 2023

The Journal of Physiology

View full text Add to dashboard Cite

The physiological consequences of stress often manifest in the gastrointestinal tract. Traumatic or chronic stress is associated with widespread maladaptive changes throughout the gut, although comparatively little is known about the effects of acute stress. Furthermore, these stress‐induced changes in the gut may increase susceptibility to gastrointestinal disorders and infection, and impact critical features of the neural and behavioural consequences of the stress response by impairing gut–brain axis communication. Understanding the mechanisms behind changes in enteric nervous system circuitry, visceral sensitivity, gut barrier function, permeability, and the gut microbiota following stress is an important research objective with pathophysiological implications in both neurogastroenterology and psychiatry. Moreover, the gut microbiota has emerged as a key aspect of physiology sensitive to the effects of stress. In this review, we focus on different aspects of the gastrointestinal tract including gut barrier function as well as the immune, humoral and neuronal elements involved in gut–brain communication. Furthermore, we discuss the evidence for a role of stress in gastrointestinal disorders. Existing gaps in the current literature are highlighted, and possible avenues for future research with an integrated physiological perspective have been suggested. A more complete understanding of the spatial and temporal dynamics of the integrated host and microbial response to different kinds of stressors in the gastrointestinal tract will enable full exploitation of the diagnostic and therapeutic potential in the fast‐evolving field of host–microbiome interactions. image

show abstract

Sympathetic Pathways Target Cholinergic Neurons in the Human Colonic Myenteric Plexus

Cited by 9 publications

References 42 publications

Catecholaminergic axon innervation and morphology in flat‐mounts of atria and ventricles of mice

Catecholaminergic axon innervation and morphology in flat‐mounts of atria and ventricles of mice

Characterisation of parasympathetic ascending nerves in human colon

The impact of acute and chronic stress on gastrointestinal physiology and function: a microbiota–gut–brain axis perspective

Contact Info

Product

Resources

About