Highly Selective Brain-to-Gut Communication via Genetically-Defined Vagus Neurons
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ABSTRACT:
PROVIDER: PRJNA723274 | ENA |
REPOSITORIES: ENA
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Project description:The vagus nerve innervates many organs, and most if not all of its motor fibers are cholinergic. However, no one knows its organizing principles; whether or not there are dedicated neurons with restricted targets that act as "labeled lines" to perform certain functions – including two opposing ones (gastric contraction versus relaxation). By performing unbiased transcriptional profiling of DMV cholinergic neurons, we discovered seven molecularly-distinct subtypes of motor neurons. Then, by using subtype-specific Cre driver mice, we go on to show that two of these subtypes exclusively innervate the glandular domain of the stomach where, remarkably, they contact different enteric neurons releasing functionally opposing neurotransmitters (acetylcholine versus nitric oxide). Thus, the vagus motor nerve communicates via genetically-defined labeled lines to control functionally unique enteric neurons within discrete subregions of the gastrointestinal tract. This discovery provides a conceptual breakthrough on the division of labor used by the vagus motor nerve to control function.
2021-05-31 | GSE172411 | GEO
Project description:The vagus nerve innervates many organs, and most, if not all, of its motor fibers are cholinergic. However, no one knows its organizing principles-whether or not there are dedicated neurons with restricted targets that act as "labeled lines" to perform certain functions, including two opposing ones (gastric contraction versus relaxation). By performing unbiased transcriptional profiling of DMV cholinergic neurons, we discovered seven molecularly distinct subtypes of motor neurons. Then, by using subtype-specific Cre driver mice, we show that two of these subtypes exclusively innervate the glandular domain of the stomach where, remarkably, they contact different enteric neurons releasing functionally opposing neurotransmitters (acetylcholine versus nitric oxide). Thus, the vagus motor nerve communicates via genetically defined labeled lines to control functionally unique enteric neurons within discrete subregions of the gastrointestinal tract. This discovery reveals that the parasympathetic nervous system utilizes a striking division of labor to control autonomic function.
| S-EPMC8273126 | biostudies-literature
Project description:Because the vagus nerve is implicated in control of inflammation, we investigated if brain death causes impairment of the parasympathetic nervous system, hence contributing to inflammation. Brain death (BD) was induced in rats. Anaesthetised ventilated rats (NBD) served as control. Heart rate variability (HRV) was assessed by ECG. The vagus nerve was electrically stimulated (BD+STIM) during BD. Intestine, kidney, heart and liver were harvested after 6h. Affymetrix chip- analysis was performed on intestinal RNA. Quantitative PCR was performed on all organs. Serum was collected to assess TNFα concentrations. Renal transplantations were performed to address the influence of vagus nerve stimulation on graft outcome. HRV was significantly lower in BD animals. Vagus nerve stimulation inhibited the increase in serum TNFα concentrations and resulted in down-regulation of a multiplicity of pro-inflammatory genes in intestinal tissue. In renal tissue vagal stimulation significantly decreased the expression of E-selectin, IL1β and ITGA6. Renal function was significantly better in recipients that received a graft from a BD+STIM donor. Our study demonstrates impairment of the parasympathetic nervous system during BD and inhibition of serum TNFα through vagal stimulation. Vagus nerve stimulation variably affected gene expression in donor organs and improved renal function in recipients. Gene expression in brain dead (BD) induced rat (with and without vagal stimulation) was compared with that of Non brain-dead ventilated control (NBD)
2010-05-19 | E-GEOD-16483 | biostudies-arrayexpress
Project description:To find inflammatory signatures in post mortem vagus nerves of COVID-19 patients in comparisin to non-infected controls.
2023-08-21 | GSE233732 | GEO
Project description:Enhanced sensitivity to Wnts is an emerging hallmark of a subset of cancers, defined in part by mutations regulating the abundance of their receptors. Inhibition of Wnt secretion by blocking an essential post-translational modification, palmitoleation, provides a useful therapeutic intervention. Inhibition of PORCN in RSPO3-translocated cancers via treatment with ETC-159 causes a marked remodeling of the transcriptome, with loss of cell cycle, stem cell, and proliferation genes and an increase in differentiation markers. Inhibition of Wnt signaling by PORCN inhibition holds promise as differentiation therapy in genetically defined human cancers.
2015-08-12 | GSE69687 | GEO
Project description:Enhanced sensitivity to Wnts is an emerging hallmark of a subset of cancers, defined in part by mutations regulating the abundance of their receptors. Inhibition of Wnt secretion by blocking an essential post-translational modification, palmitoleation, provides a useful therapeutic intervention. Inhibition of PORCN in RSPO3-translocated cancers via treatment with ETC-159 causes a marked remodeling of the transcriptome, with loss of cell cycle, stem cell, and proliferation genes and an increase in differentiation markers. Inhibition of Wnt signaling by PORCN inhibition holds promise as differentiation therapy in genetically defined human cancers. RNA-seq of colorectal PDXs with confirmed R-spondin fusion genes. RNA-seq was performed in 2 conditions (Vehicle and treatment with ETC-159 (an inhibitor of PORCN) with 4 replicates per condition.
2015-08-12 | E-GEOD-69687 | biostudies-arrayexpress
Project description:Because the vagus nerve is implicated in control of inflammation, we investigated if brain death causes impairment of the parasympathetic nervous system, hence contributing to inflammation. Brain death (BD) was induced in rats. Anaesthetised ventilated rats (NBD) served as control. Heart rate variability (HRV) was assessed by ECG. The vagus nerve was electrically stimulated (BD+STIM) during BD. Intestine, kidney, heart and liver were harvested after 6h. Affymetrix chip- analysis was performed on intestinal RNA. Quantitative PCR was performed on all organs. Serum was collected to assess TNFα concentrations. Renal transplantations were performed to address the influence of vagus nerve stimulation on graft outcome. HRV was significantly lower in BD animals. Vagus nerve stimulation inhibited the increase in serum TNFα concentrations and resulted in down-regulation of a multiplicity of pro-inflammatory genes in intestinal tissue. In renal tissue vagal stimulation significantly decreased the expression of E-selectin, IL1β and ITGA6. Renal function was significantly better in recipients that received a graft from a BD+STIM donor. Our study demonstrates impairment of the parasympathetic nervous system during BD and inhibition of serum TNFα through vagal stimulation. Vagus nerve stimulation variably affected gene expression in donor organs and improved renal function in recipients.
2009-12-01 | GSE16483 | GEO
Project description:In France, new cancer cases keep on increasing with around 150 000 deaths yearly. Cancer therapy research is constantly evolving. Indeed, several studies explore new treatments or their combination with conventional cancer treatments. But, at the same time, complementary and alternative medicines, as osteopathy, remain little explored upon their role in the combination with conventional therapy.
Several studies showed indirect interaction between vagus nerve and cancer. Firstly, vagus nerve regulates homeostasis and immunity by reducing systemic inflammation while maintaining local inflammation and antitumor effects. Secondly, vagus nerve stimulation increases Heart Rate Variability (HRV). Moreover, a higher HRV is associated with an improvement of vital prognosis in cancer patients. Vagus nerve could be stimulated by noninvasive osteopathic manipulations.
This prospective, monocentric and randomized study is a collaboration between the Centre Hospitalier d’Avignon and the Institut de Formation en Ostéopathie du Grand Avignon. It focuses on using noninvasive osteopathic mobilizations to stimulate vagus nerve. Indeed, this study aims to evaluate effects of vagus nerve osteopathic stimulations on HRV in patients with lung cancer, colorectal cancer, Non Hodgkin Lymphoma or Multiple Myeloma. More specifically, this study will tell us whether vagus nerve noninvasive osteopathic stimulations induce increase of HRV associated with a decrease of systemic inflammation and an improvement of patient’s quality of life.
| 2364606 | ecrin-mdr-crc
Project description:Purpose: To decipher the mechanisms responsible for the protective function of vagus nerve stimulation. Methods: Blood was collected from Control and Treated patients followed by isolation of PBMC'S. Total RNA was extracted and RNA sequencing was done following standard protocols Results: Detailed analysis of the transcriptomic data show that anti-inflammatory responses were upregulated in the treated samples. Conclusions: This study showed the protective role of vagus nerve stimulation in epilepsy patients.
2023-03-01 | GSE210043 | GEO
Project description:We describe a method to identify neuropeptides in specific cell-types by the conditional disruption of the gene for carboxypeptidase E (Cpe), an essential neuropeptide-processing enzyme. The loss of Cpe led to the accumulation of neuropeptides containing C-terminal basic residues which are used as tags for affinity-purification followed by identification using quantitative peptidomics. This approach enables the identification of specific forms of neuropeptides in genetically defined populations of cells.
2020-11-20 | PXD020999 | Pride