Effects of Ischemia and Reperfusion on Subpopulations of Rat Enteric Neurons Expressing the P2X7 Receptor

Palombit, Kelly; Mendes, Cristina Eusébio; Tavares-de-Lima, Wothan; Silveira, Mariana Póvoa; Castelucci, Patrícia

doi:10.1007/s10620-013-2847-y

Cited by 40 publications

(45 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Various studies have recently reported a wide range of actions of P2X7 in enteric neurons. First, P2X7 expression has been reported to be widely expressed in enteric neurons [45,46]. Activation of P2X7 has been shown to increase neuronal excitability [45], as well as being responsible for neuronal death induced by inflammation [47].…”

Section: Discussionmentioning

confidence: 99%

Modulation of lipopolysaccharide-induced neuronal response by activation of the enteric nervous system

Coquenlorge

Duchalais

Chevalier

et al. 2014

J Neuroinflammation

View full text Add to dashboard Cite

BackgroundEvidence continues to mount concerning the importance of the enteric nervous system (ENS) in controlling numerous intestinal functions in addition to motility and epithelial functions. Nevertheless, little is known concerning the direct participation of the ENS in the inflammatory response of the gut during infectious or inflammatory insults. In the present study we analyzed the ENS response to bacterial lipopolysaccharide, in particular the production of a major proinflammatory cytokine, tumor necrosis factor-alpha (TNF-α).MethodsTNF-α expression (measured by qPCR, quantitative Polymerase Chain Reaction) and production (measured by ELISA) were measured in human longitudinal muscle-myenteric plexus (LMMP) and rat ENS primary cultures (rENSpc). They were either treated or not treated with lipopolysaccharide (LPS) in the presence or not of electrical field stimulation (EFS). Activation of extracellular signal-regulated kinase (ERK) and 5’-adenosine monophosphate-activated protein kinase (AMPK) pathways was analyzed by immunocytochemistry and Western blot analysis. Their implications were studied using specific inhibitors (U0126, mitogen-activated protein kinase kinase, MEK, inhibitor and C compound, AMPK inhibitor). We also analyzed toll-like receptor 2 (TLR2) expression and interleukin-6 (IL-6) production after LPS treatment simultaneously with EFS or TNF-α-neutralizing antibody.ResultsTreatment of human LMMP or rENSpc with LPS induced an increase in TNF-α production. Activation of the ENS by EFS significantly inhibited TNF-α production. This regulation occurred at the transcriptional level. Signaling analyses showed that LPS induced activation of ERK but not AMPK, which was constitutively activated in rENSpc neurons. Both U0126 and C compound almost completely prevented LPS-induced TNF-α production. In the presence of LPS, EFS inhibited the ERK and AMPK pathways. In addition, we demonstrated using TNF-α-neutralizing antibody that LPS-induced TNF-α production increased TLR2 expression and reduced IL-6 production.ConclusionsOur results show that LPS induced TNF-α production by enteric neurons through activation of the canonical ERK pathway and also in an AMPK-dependent manner. ENS activation through the inhibition of these pathways decreased TNF-α production, thereby modulating the inflammatory response induced by endotoxin.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-014-0202-7) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Modulation of lipopolysaccharide-induced neuronal response by activation of the enteric nervous system

Coquenlorge

Duchalais

Chevalier

et al. 2014

J Neuroinflammation

View full text Add to dashboard Cite

show abstract

“…The presence of the P2X7 receptor in the myenteric neurons of DT dogs suggests its participation in many cellular processes, such as cell death and cell degeneration (Burnstock, 2014;Sperl agh and Illes, 2014). Other studies showed changes in the expression of this receptor, which was previously demonstrated in other animal species to be diminished in diseases such as intestinal ischemia/reperfusion (Paulino et al, 2011;Palombit et al, 2013), ulcerative colitis (Da Silva et al, 2015) and malnutrition (Girotti et al, 2013). However, to evaluate changes in P2X7 receptor expression in DT animals, it would be interesting to compare DT animals with control animals.…”

Section: Discussionmentioning

confidence: 84%

“…Girotti et al () demonstrated that the neuronal profile areas of NOS‐IR and ChAT neurons in the control rat distal colon were 207 and 198 μm 2 , respectively. Palombit et al () demonstrated that, in the ileum of control rats, the area profile was 411 µm 2 in ChAT‐IR neurons and 607 µm 2 in NOS‐IR neurons. Following ischemia and reperfusion, the value for ChAT‐IR neurons was 341 μm 2 , and that for NOS‐IR neurons was 577 μm 2 .…”

Section: Discussionmentioning

confidence: 99%

Morphological Characterization of the Myenteric Plexus of the Ileum and Distal colon of Dogs Affected by Muscular Dystrophy

Schäfer

Silveira

Palombit

et al. 2017

The Anatomical Record

Self Cite

View full text Add to dashboard Cite

Duchenne-like muscular dystrophy (canine dystrophinopathy) is a hereditary degenerative disease characterized by muscle changes similar to those described for Duchenne muscular dystrophy (DMD) and by alterations in the smooth muscles of the gastrointestinal tract. Some authors have suggested that these abnormalities may be associated with intestinal motility. This study analyzed the nitrergic and cholinergic neurons and P2X7 receptor expression in the myenteric plexus of the ileum and distal colon of dogs with muscular dystrophy. Immunohistochemical techniques were used to detect nitric oxide synthase (NOS) and acetylcholine transferase (ChAT) expression and to label all HuC/D- and P2X7 receptor-immunoreactive (IR) neurons. Transmission electron microscopy and basic histology were performed for further analysis. The results showed that nitrergic neurons exhibited a Dogiel type I morphology in the ileum and distal colon. The neuronal profile results showed that there were fewer NOS-, ChAT-, and HuC/D-IR neurons in the ileum than in the distal colon in the dystrophic (DT) dogs. Additionally, there were more NOS-, ChAT- and HuC/D-IR neurons per ganglion in the distal colon than in the ileum. The P2X7 receptor-expressing neurons colocalized with nitrergic and cholinergic neurons. Transmission and light microscopy revealed collagen between the muscle fibers, between the circular and longitudinal muscle layers and within the myenteric ganglia of dogs with muscular dystrophy. These findings provide a morphological description of the myenteric neurons in the ileum and distal colon of these DT dogs and may contribute to a better understanding of the gastrointestinal disorders found in patients with DMD. Anat Rec, 301:673-685, 2018. © 2017 Wiley Periodicals, Inc.

show abstract

“…Furness [26] (2006) emphasized that NOS catalyzes the formation of the NO that is present in the myenteric plexus and neuronal processes in the gut, which acts to relax the muscle fiber function of the gastrointestinal musculature. Previous studies have shown the presence of NOS in the enteric ganglia and muscle fibers under various conditions, such as malnutrition and renutrition [27,28] , ischemia and reperfusion [29][30][31] and obesity [32,33] . The enteric neurons of the ICJ stain positive for NOS, PGP 9.5, and c-kit [3,4,6,8] .…”

Section: Semmentioning

confidence: 99%

Effects of aging on the architecture of the ileocecal junction in rats

Brito

Chopard

Cury

et al. 2016

WJGPT

Self Cite

View full text Add to dashboard Cite

AIM:To evaluate the structural organization of the elastic and collagen fibers in the region of the ileocecal transition in 30 young and old male Wistar rats. METHODS:Histology, immunohistochemistry (IHC), transmission electron microscopy and scanning electron microscopy were employed in this study. The results demonstrated that there was a demarcation of the ileocecal region between the ileum and the cecum in both groups. RESULTS:The connective tissue fibers had different distribution patterns in the two groups. IHC revealed the presence of nitric oxide synthase, enteric neurons and smooth muscle fibers in the ileocecal junctions (ICJs) of both groups. Compared to the young group, the elderly group exhibited an increase in collagen type Ⅰ fibers, a decrease in collagen type Ⅲ fibers, a decreased linear density of oxytalan elastic fibers, and a greater linear density of elaunin and mature elastic fibers. CONCLUSION:The results revealed changes in the patterns of distribution of collagen and elastic fibers that may lead to a possible decrease in ICJ functionality. Core tip: The ileocolonic sphincter controls the forward and backward flow by integrating its motility with that of the distal ileum and proximal the ileocolonic sphincter controls the forward and backward flow by integrating its motility with that of the distal ileum and proxima. The ileocecal junction (ICJ) includes the muscle bundles in the terminal ileum, the intrinsic nerve plexus. The ICJ includes the muscle bundles in the terminal ileum, the intrinsic nerve plexus. Given the importance of knowing how the ICJ changes with age, the objective of this study was to characterize the morphological changes in the ICJ in rats aged 21 d and 2 years, using optical microscopy and electronic scanning and transmission methodologies. Additionally, the neurochemical characterization of the inhibitory neurons of the myenteric plexus, which are immunoreactive to the enzyme nitric oxide synthase, and the staining of the neuronal population were employed to identify immunoreactivity to HuC/D.de Brito MC, Chopard RP, Cury DP, Watanabe IS, Mendes CE, Castelucci P. Effects of aging on the architecture of the ileocecal junction in rats.

show abstract

Effects of Ischemia and Reperfusion on Subpopulations of Rat Enteric Neurons Expressing the P2X7 Receptor

Abstract: This work demonstrates that I/R is associated with a significant loss of different subpopulations of neurons in the myenteric plexus accompanied by morphological changes, all of which may underlie conditions related to intestinal motility disorder.

Cited by 40 publications

References 38 publications

Modulation of lipopolysaccharide-induced neuronal response by activation of the enteric nervous system

Modulation of lipopolysaccharide-induced neuronal response by activation of the enteric nervous system

Morphological Characterization of the Myenteric Plexus of the Ileum and Distal colon of Dogs Affected by Muscular Dystrophy

Effects of aging on the architecture of the ileocecal junction in rats

Contact Info

Product

Resources

About