Cholinergic Control of Inflammation, Metabolic Dysfunction, and Cognitive Impairment in Obesity-Associated Disorders: Mechanisms and Novel Therapeutic Opportunities DOI Creative Commons
Eric H. Chang, Sangeeta S. Chavan, Valentin A. Pavlov

et al.

Frontiers in Neuroscience, Journal Year: 2019, Volume and Issue: 13

Published: April 5, 2019

Obesity and obesity-associated disorders have become world-wide epidemics, substantially increasing the risk of debilitating morbidity mortality. A characteristic feature these disorders, which include metabolic syndrome (MetS) type 2 diabetes, is chronic low-grade inflammation stemming from immune dysregulation. Inflammation in CNS (neuroinflammation) cognitive impairment also been associated with obesity-driven disorders. The nervous system has a documented role regulation homeostasis function, recent studies indicated important vagus nerve brain cholinergic signaling this context. In review, we outline relevant aspects specific focus on conditions. We accumulating preclinical evidence for therapeutic efficacy stimulation alleviating inflammation, neuroinflammation derangements. Recently demonstrated beneficial effects galantamine, centrally-acting drug enhancer, patients MetS are summarized. These provide rationale further developments using pharmacological bioelectronic modulation benefit

Language: Английский

The gut-brain axis: is intestinal inflammation a silent driver of Parkinson’s disease pathogenesis? DOI Creative Commons
Madelyn C. Houser, Malú G. Tansey

npj Parkinson s Disease, Journal Year: 2017, Volume and Issue: 3(1)

Published: Jan. 11, 2017

Abstract The state of the intestinal environment can have profound effects on activity central nervous system through physiological contributions microbiota, regulation barrier function, and altered peripheral neurons. common language employed for much gut-brain communication is modulation immune activity. Chronic proinflammatory increasingly being recognized as a fundamental element neurodegenerative disorders, in Parkinson’s disease, inflammation intestine appears particularly relevant pathogenesis. We review evidence that dysfunction present disease it may reflect earliest manifestations pathology, we link these findings to dysregulated Based this, model pathogenesis which disorder originates progresses with its underlying mechanism. More in-depth investigations into mechanisms pre-motor symptoms are expected lead development novel diagnostic therapeutic measures slow or limit progression more advanced stages involving debilitating motor cognitive symptoms.

Language: Английский

Citations

475

Anti‐inflammatory properties of the vagus nerve: potential therapeutic implications of vagus nerve stimulation DOI Open Access
Bruno Bonaz,

Valérie Sinniger,

Sonia Pellissier

et al.

The Journal of Physiology, Journal Year: 2016, Volume and Issue: 594(20), P. 5781 - 5790

Published: April 10, 2016

Brain and viscera interplay within the autonomic nervous system where vagus nerve (VN), containing approximately 80% afferent 20% efferent fibres, plays multiple key roles in homeostatic regulations of visceral functions. Recent data have suggested anti-inflammatory role VN. This vagal function is mediated through several pathways, some them still debated. The first one hypothalamic-pituitary-adrenal axis which stimulated by fibres leads to release cortisol adrenal glands. second one, called cholinergic pathway, that synapse onto enteric neurons acetylcholine (ACh) at synaptic junction with macrophages. ACh binds α-7-nicotinic receptors those macrophages inhibit tumour necrosis (TNF)α, a pro-inflammatory cytokine. last pathway splenic sympathetic VN stimulates nerve. Norepinephrine (noradrenaline) released distal end links β2 adrenergic receptor lymphocytes ACh. Finally, inhibits TNFα spleen receptors. Understanding these pathways interesting from therapeutic point view, since they could be targeted various ways stimulate regulation TNFα-related diseases such as inflammatory bowel disease rheumatoid arthritis. Among others, stimulation, either an invasive or non-invasive procedure, becoming increasingly frequent clinical trials are ongoing evaluate potential effectiveness this therapy alleviate chronic inflammation.

Language: Английский

Citations

458

Neural regulation of immunity: molecular mechanisms and clinical translation DOI
Valentin A. Pavlov, Kevin J. Tracey

Nature Neuroscience, Journal Year: 2017, Volume and Issue: 20(2), P. 156 - 166

Published: Jan. 16, 2017

Language: Английский

Citations

425

Molecular and Functional Neuroscience in Immunity DOI Open Access
Valentin A. Pavlov, Sangeeta S. Chavan, Kevin J. Tracey

et al.

Annual Review of Immunology, Journal Year: 2018, Volume and Issue: 36(1), P. 783 - 812

Published: April 20, 2018

The nervous system regulates immunity and inflammation. molecular detection of pathogen fragments, cytokines, other immune molecules by sensory neurons generates immunoregulatory responses through efferent autonomic neuron signaling. functional organization this neural control is based on principles reflex regulation. Reflexes involving the vagus nerve nerves have been therapeutically explored in models inflammatory autoimmune conditions, recently clinical settings. brain integrates neuro-immune communication, function altered diseases characterized peripheral dysregulation Here we review anatomical basis interface with immunity, focusing functions role model immunological homunculus. Clinical advances stemming from knowledge within framework bioelectronic medicine are also briefly outlined.

Language: Английский

Citations

384

Dysbiosis of gut microbiota and microbial metabolites in Parkinson’s Disease DOI
Meng‐Fei Sun, Yan‐Qin Shen

Ageing Research Reviews, Journal Year: 2018, Volume and Issue: 45, P. 53 - 61

Published: April 26, 2018

Language: Английский

Citations

347

Multifaceted interactions between adaptive immunity and the central nervous system DOI Open Access
Jonathan Kipnis

Science, Journal Year: 2016, Volume and Issue: 353(6301), P. 766 - 771

Published: Aug. 18, 2016

Neuroimmunologists seek to understand the interactions between central nervous system (CNS) and immune system, both under homeostatic conditions in diseases. Unanswered questions include those relating diversity specificity of meningeal T cell repertoire; routes taken by cells that patrol meninges healthy invade parenchyma during pathology; opposing effects (beneficial or detrimental) these on CNS function; role after injury; evolutionary link two systems, resulting their tight interaction interdependence. This Review summarizes current standing challenging related adaptive immunity considers possible directions which aspects neuroimmunology will be heading over next decade.

Language: Английский

Citations

323

The Vagus Nerve in Appetite Regulation, Mood, and Intestinal Inflammation DOI Creative Commons
Kirsteen N. Browning, Simon Verheijden, Guy E. Boeckxstaens

et al.

Gastroenterology, Journal Year: 2016, Volume and Issue: 152(4), P. 730 - 744

Published: Dec. 15, 2016

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

Language: Английский

Citations

277

NGF and Its Receptors in the Regulation of Inflammatory Response DOI Open Access
Gaetana Minnone, Fabrizio De Benedetti, Luisa Bracci‐Laudiero

et al.

International Journal of Molecular Sciences, Journal Year: 2017, Volume and Issue: 18(5), P. 1028 - 1028

Published: May 11, 2017

There is growing interest in the complex relationship between nervous and immune systems how its alteration can affect homeostasis result development of inflammatory diseases. A key mediator cross-talk two nerve growth factor (NGF), which influence both neuronal cell function activity. The up-regulation NGF described inflamed tissues many diseases regulate innervation activity peripheral neurons, inducing release immune-active neuropeptides neurotransmitters, but also directly innate adaptive responses. Expression receptors tropomyosin receptor kinase (TrkA) p75 neurotrophin (p75NTR) dynamically regulated cells, suggesting a varying requirement for depending on their state differentiation functional has variety effects that be either pro-inflammatory or anti-inflammatory. This apparent contradiction explained by considering as part an endogenous mechanism that, while activating responses, activates pathways necessary to dampen response limit tissue damage. Decreases TrkA expression, such recently demonstrated cells arthritis patients, might prevent activation regulatory feed-back mechanisms, thus contributing maintenance chronic inflammation.

Language: Английский

Citations

269

Cholinergic modulation of the immune system presents new approaches for treating inflammation DOI
Donald B. Hoover

Pharmacology & Therapeutics, Journal Year: 2017, Volume and Issue: 179, P. 1 - 16

Published: May 18, 2017

Language: Английский

Citations

246

Breath of Life: The Respiratory Vagal Stimulation Model of Contemplative Activity DOI Creative Commons
Roderik J. S. Gerritsen, Guido P. H. Band

Frontiers in Human Neuroscience, Journal Year: 2018, Volume and Issue: 12

Published: Oct. 9, 2018

Contemplative practices, such as meditation and yoga, are increasingly popular among the general public topics of research. Beneficial effects associated with these practices have been found on physical health, mental health cognitive performance. However, studies theories that clarify underlying mechanisms lacking or scarce. This theoretical review aims to address compensate this scarcity. We will show various contemplative activities in common breathing is regulated attentively guided. respiratory discipline turn could parsimoniously explain benefits through changes autonomic balance. propose a neurophysiological model explains how specific respiration styles operate, by phasically tonically stimulating vagal nerve: nerve stimulation (rVNS). The nerve, proponent parasympathetic nervous system (PNS), prime candidate explaining cognition. discuss implications limitations our model.

Language: Английский

Citations

213