scholarly journals The 5-HT3 receptor affects rotavirus-induced motility

2021 ◽  
Author(s):  
Marie Hagbom ◽  
Arash Hellysaz ◽  
Claudia Istrate ◽  
Johan Nordgren ◽  
Sumit Sharma ◽  
...  

Rotavirus infection is highly prevalent in children, and the most severe effects are diarrhea and vomiting. It is well accepted that the enteric nervous system (ENS) is activated and plays an important role, but knowledge of how rotavirus activates nerves within ENS and to the vomiting center is lacking. Serotonin is released during rotavirus infection and antagonists to the serotonin receptor subtype 3 (5-HT3 receptor) can attenuate rotavirus-induced diarrhea. In this study we used a 5-HT3 receptor knockout (KO) mouse model to investigate the role of this receptor in rotavirus-induced diarrhea, motility, electrolyte secretion, inflammatory response and vomiting reflex. The number of diarrhea days (p=0.03) and the number of mice with diarrhea were lower in infected 5-HT3 receptor KO than wildtype pups. In vivo investigation of FITC-dextran transit time showed that intestinal motility was lower in the infected 5-HT3 receptor KO compared to wildtype mice (p=0.0023). Ex vivo Ussing chamber measurements of potential difference across the intestinal epithelia showed no significant difference in electrolyte secretion between the two groups. Immediate early gene cFos expression level showed no difference in activation of the vomiting center in the brain. Cytokine analysis of the intestine indicating low effect of inflammatory response in rotavirus-infected mice lacking the 5-HT3 receptor. Our findings indicate that the 5-HT3 receptor is involved in rotavirus-induced diarrhea via its effect on intestinal motility and that the vagus nerve signaling to the vomiting center occurs also in the absence of the 5-HT3 receptor. IMPORTANCE The mechanisms underlying rotavirus-induced diarrhea and vomiting are not yet fully understood. To better understand rotavirus pathophysiology, characterization of nerve signaling within the ENS and trough vagal efferent nerves to the brain, which have been shown to be of great importance to the disease, is necessary. Serotonin (5-HT), a mediator of both diarrhea and vomiting, has been shown to be released from enterochromaffin cells in response to rotavirus infection and the rotavirus enterotoxin NSP4. Here, we investigated the role of the serotonin receptor 5-HT3, which is known to be involved in the nerve signals that regulate gut motility, intestinal secretion, and signal transduction through the vagus nerve to the brain. We show that the 5-HT3 receptor is involved in rotavirus-induced diarrhea by promoting intestinal motility. The findings shed light on new treatment possibilities for rotavirus diarrhea.

Author(s):  
Andrea Sanchez-Navarro ◽  
Isaac González-Soria ◽  
Rebecca Caldiño-Bohn ◽  
Norma A. Bobadilla

Serpins are a superfamily of proteins characterized by their common function as serine protease inhibitors. So far, 36 serpins from nine clades have been identified. These proteins are expressed in all the organs and are involved in multiple important functions such as the regulation of blood pressure, hormone transport, insulin sensitivity, and the inflammatory response. Diseases such as obesity, diabetes, cardiovascular, and kidney disorders are intensively studied to find effective therapeutic targets. Given serpins' outstanding functionality, the deficiency or overexpression of certain types of serpin have been associated with diverse pathophysiological events. In particular, we will focus on reviewing the studies evaluating the participation of serpins, and particularly SerpinA3, in diverse diseases that occur in relevant organs such as the brain, retinas, corneas, lungs, cardiac vasculature, and kidneys. In this review, we summarize the role of serpins in physiological and pathophysiological processes, as well as recent evidence on the crucial role of SerpinA3 in several pathologies. Finally, we emphasize the importance of SerpinA3 in regulating cellular processes such as angiogenesis, apoptosis, fibrosis, oxidative stress, and the inflammatory response.


2017 ◽  
Vol 41 (S1) ◽  
pp. S638-S638
Author(s):  
T. Schwitzer ◽  
R. Schwan ◽  
A. Giersch ◽  
E. Albuisson ◽  
K. Angioi-Duprez ◽  
...  

IntroductionAlthough cannabis is very widespread worldwide, its brain toxicity is poorly understood. The neuroretina is an accessible extension of the brain and could be a relevant site for investigating neurotransmission abnormalities in neuropsychiatric disorders. The retina has a functional endocannabinoid system involved in the regulation of retinal neurotransmission. In animals, the modulation of this system led to retinal dysfunctions measured with the electroretinogram (ERG).ObjectivesTo assess whether the regular cannabis use could affect the neuroretinal function.AimsAssessments of the neuroretinal function in cannabis users compared with controls.MethodsRecordings of pattern, flash and on-off ERG were performed in 55 cannabis users and 29 controls. The amplitude and implicit time of the following waves were evaluated: N95 (pattern); a – and b – (flash); a –, b- and d1 – (on-off).ResultsCannabis users showed a significant increase in implicit time of the waves N95 (P = 0.0001), a- (P = 0.029) and b – (P = 0.002) for the flash ERG and b – (P = 0.016) and d1 – (P = 0.027) for the on-off ERG, compared with controls. No significant difference was found between groups in terms of wave's amplitudes.ConclusionsThese results show a delay in the response of cones, bipolar and ganglion cells of the on and off pathways to constitute a delay of ≈ 6 ms in the transmission of information from the retina to the brain in cannabis users. Cannabis could disrupt the regulatory role of the cannabinoid system and impair retinal glutamatergic neurotransmission. The consequences on visual perception should be explored in future studies.Disclosure of interestThe authors have not supplied their declaration of competing interest.


2015 ◽  
Vol 27 (11) ◽  
pp. 2126-2132 ◽  
Author(s):  
Roberta Sellaro ◽  
Jelle W. R. van Leusden ◽  
Klodiana-Daphne Tona ◽  
Bart Verkuil ◽  
Sander Nieuwenhuis ◽  
...  

People tend to slow down after they commit an error, a phenomenon known as post-error slowing (PES). It has been proposed that slowing after negative feedback or unforeseen errors is linked to the activity of the locus coeruleus–norepinephrine (LC–NE) system, but there is little direct evidence for this hypothesis. Here, we assessed the causal role of the noradrenergic system in modulating PES by applying transcutaneous vagus nerve stimulation (tVNS), a new noninvasive and safe method to stimulate the vagus nerve and to increase NE concentrations in the brain. A single-blind, sham-controlled, between-group design was used to assess the effect of tVNS in healthy young volunteers (n = 40) during two cognitive tasks designed to measure PES. Results showed increased PES during active tVNS, as compared with sham stimulation. This effect was of similar magnitude for the two tasks. These findings provide evidence for an important role of the noradrenergic system in PES.


2011 ◽  
Vol 238 (1-2) ◽  
pp. 44-51 ◽  
Author(s):  
Cristina Pintado ◽  
Elisa Revilla ◽  
María L. Vizuete ◽  
Sebastián Jiménez ◽  
Luisa García-Cuervo ◽  
...  

2021 ◽  
Author(s):  
Sol Beccari ◽  
Virginia Sierra-Torre ◽  
Jorge Valero ◽  
Mikel Garcia-Zaballa ◽  
Alejandro Carretero-Guillen ◽  
...  

Microglial phagocytosis is rapidly emerging as a therapeutic target in neurodegenerative and neurological disorders. An efficient removal of cellular debris is necessary to prevent buildup damage of neighbor neurons and the development of an inflammatory response. As the brain professional phagocytes, microglia are equipped with an array of mechanisms that enable them to recognize and degrade several types of cargo, including neurons undergoing apoptotic cell death. While microglia are very competent phagocytes of apoptotic cells under physiological conditions, here we report their dysfunction in mouse and monkey (Macaca fascicularis and Callithrix jacchus) models of stroke by transient occlusion of the medial cerebral artery (tMCAo). The impairment of both engulfment and degradation was related to energy depletion triggered by oxygen and nutrients deprivation (OND), which led to reduced process motility, lysosomal depletion, and the induction of a protective autophagy response in microglia. Basal autophagy, which is in charge of removing and recycling intracellular elements, was critical to maintain microglial physiology, including survival and phagocytosis, as we determined both in vivo and in vitro using knock-out models of autophagy genes and the autophagy inhibitor MRT68921. Notably, the autophagy inducer rapamycin partially prevented the phagocytosis impairment induced by tMCAo in vivo but not by OND in vitro. These results suggest a more complex role of microglia in stroke than previously acknowledged, classically related to the inflammatory response. In contrast, here we demonstrate the impairment of apoptotic cell phagocytosis, a microglial function critical for brain recovery. We propose that phagocytosis is a therapeutic target yet to be explored and provide evidence that it can be modulated in vivo using rapamycin, setting the stage for future therapies for stroke patients.


Author(s):  
S. Sunitha ◽  
◽  
A .Catherin Jayanthy ◽  
G. Kalaiyarasan ◽  
N. Annalakshmi

From the long years ago, education have been trying a proper way to improving the skills of English. Educators tried several methodologies in English to choose the better one. This paper brings out the effect of teaching Receptive skills by implementing NLP (Neuro- Linguistic Programming) in second language as English. Neuro- Linguistic Programming is one of the methods to catch up the English by giving focus on the brain anatomy. Brain anatomy can motive the creativity as well as the skills of using language. It also exist the role of Neuro Linguistic Programming in teaching the Receptive skills of English, which could make the students to improve the Receptive skills such as listening and reading. The study, in short, affirms that NLP strategies could be quite efficacious in making the students procure the skills that are indispensable in workplaces effortlessly. As it involves teaching a reading comprehension course by NLP concepts and techniques, the approach used in this study is experimental. In addition, the experimental method involves pre-and post-tests conducted before and after the course by the control group (40 students) and the experimental group (40 students). The students of the experimental community are chosen from the secondary school students. After the NLP experimentation, it was revealed from the study that there was a significant difference in the level of the experimental group in pre and post-test.


2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Haidong Wang ◽  
Pengfei Xu ◽  
Dehua Liao ◽  
Ruili Dang ◽  
Xin He ◽  
...  

Objectives. Clinical and experimental evidence has clarified that the inflammatory processes within the brain play a pivotal role in the pathophysiology of seizures and epilepsy. Inflammasomes and P2X7 purinergic receptor (P2X7R) are important mediators during the inflammatory process. Therefore, we investigated the possible association between partial seizures and inflammasomes NLPR1, NLRP3, and P2X7R gene polymorphisms in the present study. Method. A total of 163 patients and 201 health controls were enrolled in this study and polymorphisms of NLPR1, NLRP3, and P2X7R genes were detected using polymerase chain reaction- (PCR-) ligase detection reaction method. Result. The frequency of rs878329 (G>C) genotype with C (CG + CC) was significantly lower among patients with partial seizures relative to controls (OR = 2.033, 95% CI = 1.290–3.204, p=0.002 for GC + CC versus GG). Intriguingly, we found that the significant difference of rs878329 (G>C) genotype and allele frequency only existed among males (OR = 2.542, 95% CI = 1.344–4.810, p=0.004 for GC + CC versus GG), while there was no statistically significant difference among females. However, no significant results were presented for the genotype distributions of rs8079034, rs4612666, rs10754558, rs2027432, rs3751143, and rs208294 polymorphisms between patients and controls. Conclusion. Our study demonstrated the potentially significant role of NLRP1 rs878329 (G>C) in developing susceptibility to the partial seizures in a Chinese Han population.


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