Vagal innervation of the stomach reassessed: brain−gut connectome uses smart terminals

Powley, Terry L.; Jaffey, Deborah; McAdams, Jennifer L.; Baronowsky, Elizabeth A.; Black, Diana; Chesney, Logan; Evans, Charlene; Phillips, Robert

doi:10.1111/nyas.14138

Cited by 45 publications

(75 citation statements)

References 52 publications

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“…The vagus nerve, cited as the pneumogastric nerve or 10th cranial nerve, although referred in the singular is paired (right and left VN). It is the longest nerve in the body, extending from the (Powley et al, 2019). The NTS, the main entry point of the digestive tract into the brain, is located in the medulla, just above the DMNV which is at the origin of vagal efferent fibers with the nucleus ambiguus (Jean, 1991).…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Potential of Vagus Nerve Stimulation for Inflammatory Bowel Diseases

2021

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The vagus nerve is a mixed nerve, comprising 80% afferent fibers and 20% efferent fibers. It allows a bidirectional communication between the central nervous system and the digestive tract. It has a dual anti-inflammatory properties via activation of the hypothalamic pituitary adrenal axis, by its afferents, but also through a vago-vagal inflammatory reflex involving an afferent (vagal) and an efferent (vagal) arm, called the cholinergic anti-inflammatory pathway. Indeed, the release of acetylcholine at the end of its efferent fibers is able to inhibit the release of tumor necrosis factor (TNF) alpha by macrophages via an interneuron of the enteric nervous system synapsing between the efferent vagal endings and the macrophages and releasing acetylcholine. The vagus nerve also synapses with the splenic sympathetic nerve to inhibit the release of TNF-alpha by splenic macrophages. It can also activate the spinal sympathetic system after central integration of its afferents. This anti-TNF-alpha effect of the vagus nerve can be used in the treatment of chronic inflammatory bowel diseases, represented by Crohn’s disease and ulcerative colitis where this cytokine plays a key role. Bioelectronic medicine, via vagus nerve stimulation, may have an interest in this non-drug therapeutic approach as an alternative to conventional anti-TNF-alpha drugs, which are not devoid of side effects feared by patients.

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Section: Introductionmentioning

confidence: 99%

Therapeutic Potential of Vagus Nerve Stimulation for Inflammatory Bowel Diseases

2021

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“…Furthermore, not only may this provide therapeutic targets by which inappropriate immune responses may be addressed, it may also uncover avenues by which visceral hypersensitivity disorders that are exacerbated by food ingestion (such as irritable bowel syndrome and functional dyspepsia) may be alleviated. Of note, the intestinal EEC are also equipped to function as “sentinels” within the intestinal environment and release cytokines in response to microbial metabolites and pathogens [ 171 ]; the direct synaptic connection between EEC and vagal afferent nerve endings suggests an additional role for neuropods in rapid signaling of mucosal immune responses via the gut–brain axis, or even in axon reflex responses to sensory stimulation [ 172 ].…”

Section: Discussionmentioning

confidence: 99%

Central Neurocircuits Regulating Food Intake in Response to Gut Inputs—Preclinical Evidence

Browning

Carson

2021

Nutrients

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The regulation of energy balance requires the complex integration of homeostatic and hedonic pathways, but sensory inputs from the gastrointestinal (GI) tract are increasingly recognized as playing critical roles. The stomach and small intestine relay sensory information to the central nervous system (CNS) via the sensory afferent vagus nerve. This vast volume of complex sensory information is received by neurons of the nucleus of the tractus solitarius (NTS) and is integrated with responses to circulating factors as well as descending inputs from the brainstem, midbrain, and forebrain nuclei involved in autonomic regulation. The integrated signal is relayed to the adjacent dorsal motor nucleus of the vagus (DMV), which supplies the motor output response via the efferent vagus nerve to regulate and modulate gastric motility, tone, secretion, and emptying, as well as intestinal motility and transit; the precise coordination of these responses is essential for the control of meal size, meal termination, and nutrient absorption. The interconnectivity of the NTS implies that many other CNS areas are capable of modulating vagal efferent output, emphasized by the many CNS disorders associated with dysregulated GI functions including feeding. This review will summarize the role of major CNS centers to gut-related inputs in the regulation of gastric function with specific reference to the regulation of food intake.

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“…The vagal efferents consist essentially in the axons of the large cholinergic neurons stacked in the dorsal motor nucleus of the vagus ( Fig. 1 ), that project to all visceras and trigger their actions via cholinergic, local neurons located in intravisceral ganglia [ 16 ]. The synaptically interconnected afferents and efferents of the vagus nerve within the dorsal vagal complex of the brainstem yield reflex circuits that provide the anatomical substratum of the vital homeostatic regulations.…”

Section: The Vagus Nerve As a Route Of Sars-cov-2 Invasion Of The Bramentioning

confidence: 99%

The Vagal Autonomic Pathway of COVID-19 at the Crossroad of Alzheimer’s Disease and Aging: A Review of Knowledge

Rangon

Krantic

Moyse

et al. 2020

Journal of Alzheimer's Disease Reports

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Coronavirus Disease 2019 (COVID-19) pandemic-triggered mortality is significantly higher in older than in younger populations worldwide. Alzheimer’s disease (AD) is related to aging and was recently reported to be among the major risk factors for COVID-19 mortality in older people. The symptomatology of COVID-19 indicates that lethal outcomes of infection rely on neurogenic mechanisms. The present review compiles the available knowledge pointing to the convergence of COVID-19 complications with the mechanisms of autonomic dysfunctions in AD and aging. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is prone to neuroinvasion from the lung along the vagus nerve up to the brainstem autonomic nervous centers involved in the coupling of cardiovascular and respiratory rhythms. The brainstem autonomic network allows SARS-CoV-2 to trigger a neurogenic switch to hypertension and hypoventilation, which may act in synergy with aging- and AD-induced dysautonomias, along with an inflammatory “storm”. The lethal outcomes of COVID-19, like in AD and unhealthy aging, likely rely on a critical hypoactivity of the efferent vagus nerve cholinergic pathway, which is involved in lowering cardiovascular pressure and systemic inflammation tone. We further discuss the emerging evidence supporting the use of 1) the non-invasive stimulation of vagus nerve as an additional therapeutic approach for severe COVID-19, and 2) the demonstrated vagal tone index, i.e., heart rate variability, via smartphone-based applications as a non-serological low-cost diagnostic of COVID-19. These two well-known medical approaches are already available and now deserve large-scale testing on human cohorts in the context of both AD and COVID-19.

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Vagal innervation of the stomach reassessed: brain−gut connectome uses smart terminals

Cited by 45 publications

References 52 publications

Therapeutic Potential of Vagus Nerve Stimulation for Inflammatory Bowel Diseases

Therapeutic Potential of Vagus Nerve Stimulation for Inflammatory Bowel Diseases

Central Neurocircuits Regulating Food Intake in Response to Gut Inputs—Preclinical Evidence

The Vagal Autonomic Pathway of COVID-19 at the Crossroad of Alzheimer’s Disease and Aging: A Review of Knowledge

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