TNFα Causes Thrombin-Dependent Vagal Neuron Apoptosis in Inflammatory Bowel Disease

Fritze, Danielle; Zhang, Weizhen; Li, Ji Yao; Chai, Biaoxin; Mulholland, Michael W.

doi:10.1007/s11605-014-2573-6

Cited by 8 publications

(8 citation statements)

References 32 publications

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“…In addition, we found independent associations of microglial cells with the five traits (Supplementary Fig. 12e–i), providing additional support for the recently implicated role of microglia in autoimmune diseases 61–63 .…”

Section: Resultssupporting

confidence: 79%

Genetic mapping of cell type specificity for complex traits

et al. 2019

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Single-cell RNA sequencing (scRNA-seq) data allows to create cell type specific transcriptome profiles. Such profiles can be aligned with genome-wide association studies (GWASs) to implicate cell type specificity of the traits. Current methods typically rely only on a small subset of available scRNA-seq datasets, and integrating multiple datasets is hampered by complex batch effects. Here we collated 43 publicly available scRNA-seq datasets. We propose a 3-step workflow with conditional analyses within and between datasets, circumventing batch effects, to uncover associations of traits with cell types. Applying this method to 26 traits, we identify independent associations of multiple cell types. These results lead to starting points for follow-up functional studies aimed at gaining a mechanistic understanding of these traits. The proposed framework as well as the curated scRNA-seq datasets are made available via an online platform, FUMA, to facilitate rapid evaluation of cell type specificity by other researchers.

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Section: Resultssupporting

confidence: 79%

Genetic mapping of cell type specificity for complex traits

et al. 2019

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“…Calcium imaging studies suggest that TNF-a potentiates vagal afferent terminal responses, thus activates NTS neurons 78 , increases DVC microglial activation and induces DMV apoptosis via PAR1 and PAR2 receptor activation 79,80 . Vagal motoneurons are also inhibited by IL-1b, partly via local synthesis of prostaglandins 81 , suggesting that inflammation-associated GI disorders may result, at least in part, from dysregulation of both afferent and efferent VN.…”

Section: Introductionmentioning

confidence: 99%

The Vagus Nerve in Appetite Regulation, Mood, and Intestinal Inflammation

2017

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Although the gastrointestinal (GI) tract contains intrinsic neural plexuses that allow a significant degree of independent control over GI functions, the central nervous system provides extrinsic neural inputs that modulate, regulate and integrate these functions. In particular, the vagus nerve (VN) provides the parasympathetic innervation to the GI tract, co-ordinates the complex interactions between central and peripheral neural control mechanisms. This review will discuss the physiological roles of the afferent (sensory) and motor (efferent) vagus in regulation of appetite, mood and the immune system, as well as the pathophysiological outcomes of VN dysfunction resulting in obesity, mood disorders and inflammation. The therapeutic potential of VN modulation to attenuate or reverse these pathophysiological outcomes and restore autonomic homeostasis will also be discussed.

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“…The dose of SPD304 (5μg) was based on a dose (2.5μg) used for 4th cerebroventricular injection to effectively inhibit the effect of TNF-α in a previously published report. 27…”

Section: Drugs and Drug Administrationmentioning

confidence: 99%

Brain TACE (Tumor Necrosis Factor-α–Converting Enzyme) Contributes to Sympathetic Excitation in Heart Failure Rats

Cao

Bell

et al. 2019

Hypertension

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Tumor necrosis factor-α (TNF-α) is initially synthesized as a transmembrane protein that is cleaved by TNF-α converting enzyme (TACE) to release soluble TNF-α. The elevated level of TNF-α in the brain and circulation in heart failure (HF) suggests an increase in the TACEmediated ectodomain shedding process. The present study sought to determine whether TACE is upregulated in cardiovascular/autonomic brain regions like subfornical organ (SFO) and hypothalamic paraventricular nucleus (PVN) in rats with ischemia-induced HF and whether TACE plays a role in TNF-α-driven sympathetic excitation. We found that TACE was expressed throughout the SFO and PVN, with significantly higher levels in HF than in sham-operated (Sham) rats. Intracerebroventricular (ICV) injection of recombinant TACE induced a mild increase in blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) that peaked at 15-20 min in both Sham and HF rats. HF rats had a secondary prolonged increase in these variables that was prevented by the TNF-α inhibitor SPD304. ICV administration of the TACE inhibitor TAPI-1 decreased BP, HR and RSNA in Sham and HF rats, with an exaggerated reduction in HR and RSNA in the HF rats. Direct microinjection of TACE or TAPI-1 into PVN or SFO of Sham and HF rats elicited BP, HR and RSNA responses similar to ICV TACE or TAPI-1. ICV infusion of angiotensin II and interleukin-1β increased TACE expression in SFO and PVN of normal rats. These data suggest that a TACE-mediated increase in soluble TNF-α in the brain contributes to sympathetic excitation in HF.

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TNFα Causes Thrombin-Dependent Vagal Neuron Apoptosis in Inflammatory Bowel Disease

Cited by 8 publications

References 32 publications

Genetic mapping of cell type specificity for complex traits

Genetic mapping of cell type specificity for complex traits

The Vagus Nerve in Appetite Regulation, Mood, and Intestinal Inflammation

Brain TACE (Tumor Necrosis Factor-α–Converting Enzyme) Contributes to Sympathetic Excitation in Heart Failure Rats

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