Effect of modified Wendan Decoction on enteric glia cells in depression model rats

The enteric nervous system may have an important role in modulating gastrointestinal barrier response to disease through activation of enteric glia cells. In vitro studies have shown that enteric glia activation improves intestinal epithelial barrier function by altering the expression of tight junction proteins. We hypothesized that severe injury would increase expression of glial fibrillary acidic protein (GFAP), a marker of enteric glial activation. We also sought to define the effects of vagal nerve stimulation on enteric glia activation and intestinal barrier function using a model of systemic injury and local gut mucosal involvement. Mice with 30% total body surface area steam burn were used as model of severe injury. Vagal nerve stimulation was performed to assess the role of parasympathetic signaling on enteric glia activation. In vivo intestinal permeability was measured to assess barrier function. Intestine was collected to investigate changes in histology; GFAP expression was assessed by quantitative PCR, by confocal microscopy, and in GFAP-luciferase transgenic mice. Stimulation of the vagus nerve prevented injury-induced intestinal barrier injury. Intestinal GFAP expression increased at early time points following burn and returned to baseline by 24 h after injury. Vagal nerve stimulation prior to injury increased GFAP expression to a greater degree than burn alone. Gastrointestinal bioluminescence was imaged in GFAP-luciferase transgenic animals following either severe burn or vagal stimulation and confirmed the increased expression of intestinal GFAP. Injection of S-nitrosoglutathione, a signaling molecule released by activated enteric glia cells, following burn exerts protective effects similar to vagal nerve stimulation. Intestinal expression of GFAP increases following severe burn injury. Stimulation of the vagus nerve increases enteric glia activation, which is associated with improved intestinal barrier function. The vagus nerve may mediate the signaling that occurs from the central nervous system to the enteric nervous system following gastrointestinal injury.

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Interaction of Human Enterochromaffin Cells with Human Enteric Adenovirus 41 Leads to Serotonin Release and Subsequent Activation of Enteric Glia Cells

Journal of Virology ◽

10.1128/jvi.00026-18 ◽

2018 ◽

Vol 92 (7) ◽

Cited By ~ 7

Author(s):

Sonja Westerberg ◽

Marie Hagbom ◽

Anandi Rajan ◽

Vesa Loitto ◽

B. David Persson ◽

...

Keyword(s):

Acute Gastroenteritis ◽

Human Adenovirus ◽

Serotonin Release ◽

Enterochromaffin Cells ◽

Low Grade ◽

Enteric Glia ◽

Glia Cells ◽

Serotonin Secretion ◽

Enteric Adenovirus ◽

Cell Supernatant

ABSTRACTHuman adenovirus 41 (HAdV-41) causes acute gastroenteritis in young children. The main characteristics of HAdV-41 infection are diarrhea and vomiting. Nevertheless, the precise mechanism of HAdV-41-induced diarrhea is unknown, as a suitable small-animal model has not been described. In this study, we used the human midgut carcinoid cell line GOT1 to investigate the effect of HAdV-41 infection and the individual HAdV-41 capsid proteins on serotonin release by enterochromaffin cells and on enteric glia cell (EGC) activation. We first determined that HAdV-41 could infect the enterochromaffin cells. Immunofluorescence staining revealed that the cells expressed HAdV-41-specific coxsackievirus and adenovirus receptor (CAR); flow cytometry analysis supported these findings. HAdV-41 infection of the enterochromaffin cells induced serotonin secretion dose dependently. In contrast, control infection with HAdV-5 did not induce serotonin secretion in the cells. Confocal microscopy studies of enterochromaffin cells infected with HAdV-41 revealed decreased serotonin immunofluorescence compared to that in uninfected cells. Incubation of the enterochromaffin cells with purified HAdV-41 short fiber knob and hexon proteins increased the serotonin levels in the harvested cell supernatant significantly. HAdV-41 infection could also activate EGCs, as shown in the significantly altered expression of glia fibrillary acidic protein (GFAP) in EGCs incubated with HAdV-41. The EGCs were also activated by serotonin alone, as shown in the significantly increased GFAP staining intensity. Likewise, EGCs were activated by the cell supernatant of HAdV-41-infected enterochromaffin cells.IMPORTANCEThe nonenveloped human adenovirus 41 causes diarrhea, vomiting, dehydration, and low-grade fever mainly in children under 2 years of age. Even though acute gastroenteritis is well described, how human adenovirus 41 causes diarrhea is unknown. In our study, we analyzed the effect of human adenovirus 41 infection on human enterochromaffin cells and found it stimulates serotonin secretion in the cells, which is involved in regulation of intestinal secretion and gut motility and can also activate enteric glia cells, which are found in close proximity to enterochromaffin cellsin vivo. This disruption of gut barrier homeostasis as maintained by these cells following human adenovirus 41 infection might be a mechanism in enteric adenovirus pathogenesis in humans and could indicate a possible serotonin-dependent cross talk between human adenovirus 41, enterochromaffin cells, and enteric glia cells.

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Mo1590 - Purinergic Signaling in Enteric Glia Cells During Inflammation

Gastroenterology ◽

10.1016/s0016-5085(18)32641-6 ◽

2018 ◽

Vol 154 (6) ◽

pp. S-763

Author(s):

Reiner Schneider ◽

Anna Miesen ◽

Bianca Schneiker ◽

Mariola Lysson ◽

Fievos L. Christofi ◽

...

Keyword(s):

Purinergic Signaling ◽

Enteric Glia ◽

Glia Cells

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The role of enteric glia in gut inflammation

Neuron Glia Biology ◽

10.1017/s1740925x11000068 ◽

2010 ◽

Vol 6 (4) ◽

pp. 231-236 ◽

Cited By ~ 16

Author(s):

Georg von Boyen ◽

Martin Steinkamp

Keyword(s):

Chagas Disease ◽

Enteric Glia ◽

Gut Inflammation ◽

Glia Cells ◽

Mucosal Integrity ◽

Gut Homeostasis ◽

Inflammatory Bowel ◽

Lines Of Evidence ◽

Disease Complexes

A neuro-glia interaction is part of gut inflammation and essential for the integrity of the bowel. A loss of enteric glia cells (EGCs) led to a fatal haemorrhagic jejuno-ileitis and death in a few days. Although a diminished EGC network is postulated in inflammatory bowel disease and enteric glia pathology is described in Chagas' disease the role of EGCs in the onset of these disease complexes is not definitely clear. Several lines of evidence implicate that the secretion of different factors by enteric glia may be the key for modulating gut homeostasis. As mucosal integrity might be important for remission in Crohn's disease and inflammation of the enteric nervous system is part of the pathology in Chagas' disease, the role of EGCs during gut inflammation could be part of the key to understand these diseases.

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Nerve Growth Factor Secretion in Cultured Enteric Glia Cells is Modulated by Proinflammatory Cytokines

Journal of Neuroendocrinology ◽

10.1111/j.1365-2826.2006.01478.x ◽

2006 ◽

Vol 18 (11) ◽

pp. 820-825 ◽

Cited By ~ 34

Author(s):

G. B. T. von Boyen ◽

M. Steinkamp ◽

M. Reinshagen ◽

K.-H. Schäfer ◽

G. Adler ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Proinflammatory Cytokines ◽

Enteric Glia ◽

Nerve Growth ◽

Glia Cells ◽

Factor Secretion ◽

Growth Factor Secretion

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Enteric Glia Cells Attenuate Cytomix-Induced Intestinal Epithelial Barrier Breakdown

Journal of Surgical Research ◽

10.1016/j.jss.2011.11.272 ◽

2012 ◽

Vol 172 (2) ◽

pp. 202-203

Author(s):

G.A. Cheadle ◽

T.W. Costantini ◽

A. Hageny ◽

J.G. Putnam ◽

N. Lopez ◽

...

Keyword(s):

Epithelial Barrier ◽

Intestinal Epithelial ◽

Intestinal Epithelial Barrier ◽

Enteric Glia ◽

Glia Cells ◽

Barrier Breakdown

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Enteric glia cells are critical to limiting the intestinal inflammatory response after injury

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00371.2016 ◽

2017 ◽

Vol 312 (3) ◽

pp. G274-G282 ◽

Cited By ~ 15

Author(s):

Simone Langness ◽

Mitsuaki Kojima ◽

Raul Coimbra ◽

Brian P. Eliceiri ◽

Todd W. Costantini

Keyword(s):

Intestinal Permeability ◽

Nerve Stimulation ◽

Immune Cells ◽

Immune Cell ◽

Intestinal Inflammation ◽

Direct Connection ◽

Enteric Glia ◽

Cell Recruitment ◽

Glia Cells ◽

Immune Cell Recruitment

Vagal nerve stimulation (VNS) has been shown to limit intestinal inflammation following injury; however, a direct connection between vagal terminals and resident intestinal immune cells has yet to be identified. We have previously shown that enteric glia cell (EGC) expression is increased after injury through a vagal-mediated pathway to help restore gut barrier function. We hypothesize that EGCs modulate immune cell recruitment following injury and relay vagal anti-inflammatory signals to resident immune cells in the gut. EGCs were selectively ablated from an isolated segment of distal bowel with topical application of benzalkonium chloride (BAC) in male mice. Three days following BAC application, mice were subjected to an ischemia-reperfusion injury (I/R) by superior mesenteric artery occlusion for 30 min. VNS was performed in a separate cohort of animals. EGC+ and EGC− segments were compared utilizing histology, flow cytometry, immunohistochemistry, and intestinal permeability. VNS significantly reduced immune cell recruitment after I/R injury in EGC+ segments with cell percentages similar to sham. VNS failed to limit immune cell recruitment in EGC− segments. Histologic evidence of gut injury was diminished with VNS application in EGC+ segments, whereas EGC− segments showed features of more severe injury. Intestinal permeability increased following I/R injury in both EGC+ and EGC− segments. Permeability was significantly lower after VNS application compared with injury alone in EGC+ segments only (95.1 ± 30.0 vs. 217.6 ± 21.7 μg/ml, P < 0.05). Therefore, EGC ablation uncouples the protective effects of VNS, suggesting that vagal-mediated signals are translated to effector cells through EGCs. NEW & NOTEWORTHY Intestinal inflammation is initiated by local immune cell activation and epithelial barrier breakdown, resulting in the production of proinflammatory mediators with subsequent leukocyte recruitment. Vagal nerve stimulation (VNS) has been shown to limit intestinal inflammation following injury; however, direct connection between vagal terminals and resident intestinal immune cells has yet to be identified. Here, we demonstrate that intact enteric glia cells are required to transmit the gut anti-inflammatory effects of VNS.

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