Neural Regulation of Hematopoiesis, Inflammation, and Cancer

Hanoun, Maher; Maryanovich, Maria; Arnal-Estapé, Anna; Frenette, Paul S.

doi:10.1016/j.neuron.2015.01.026

Cited by 211 publications

(188 citation statements)

References 153 publications

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“…The synaptic plasticity that we have identified in the adrenal may be involved in other conditions that involve robust sympathetic activation (11). For example, the baroreceptor reflex activates preganglionic neurons innervating norepinephrinesecreting chromaffin cells (47).…”

Section: Discussionmentioning

confidence: 96%

“…These findings reveal a critical role for sympatho-adrenal synaptic plasticity in the CRR to hypoglycemia, and suggest that a failure to induce synaptic strengthening may lead to conditions associated with a loss of glycemic control (1, 3). More broadly, this type of sympathetic plasticity could regulate the activity of a growing list of unconventional autonomic targets, including hematopoietic stem cells and bone osteoblasts (11,12). …”

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confidence: 99%

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Fasting induces a form of autonomic synaptic plasticity that prevents hypoglycemia

Wang

Whim

2016

Proc. Natl. Acad. Sci. U.S.A.

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During fasting, activation of the counter-regulatory response (CRR) prevents hypoglycemia. A major effector arm is the autonomic nervous system that controls epinephrine release from adrenal chromaffin cells and, consequently, hepatic glucose production. However, whether modulation of autonomic function determines the relative strength of the CRR, and thus the ability to withstand food deprivation and maintain euglycemia, is not known. Here we show that fasting leads to altered transmission at the preganglionic → chromaffin cell synapse. The dominant effect is a presynaptic, long-lasting increase in synaptic strength. Using genetic and pharmacological approaches we show this plasticity requires neuropeptide Y, an adrenal cotransmitter and the activation of adrenal Y5 receptors. Loss of neuropeptide Y prevents a fasting-induced increase in epinephrine release and results in hypoglycemia in vivo. These findings connect plasticity within the sympathetic nervous system to a physiological output and indicate the strength of the final synapse in this descending pathway plays a decisive role in maintaining euglycemia.hypoglycemia | autonomic nervous system | synaptic plasticity | adrenal | chromaffin cells F ailure to avoid hypoglycemia can lead to dysphoria, ventricular arrhythmia, and even sudden death (1). That these effects are rare and observed only in response to prolonged fasting or severe insulin-induced hypoglycemia is because of the remarkable effectiveness of the counter-regulatory response (CRR). This sensory-motor homeostatic feedback loop detects a fall in blood glucose through central and peripheral receptors and initiates a neuronal, endocrine, and behavioral response that restores euglycemia (2). One of the principal effector arms of the CRR is the sympatho-adrenal branch of the autonomic nervous system. Hypoglycemia elevates sympathetic activity, increasing hepatic glucose production and the release of gluconeogenic substrates while suppressing insulin and potentiating glucagon secretion (3, 4).During fasting, these autonomic actions are mediated by epinephrine, which enters the systemic circulation after release from adrenal neuroendocrine chromaffin cells and by norepinephrine, secreted directly onto target tissues from postganglionic sympathetic neurons. The importance of sympathetic activity, and in particular circulating epinephrine in the CRR, is illustrated by the poor recovery from insulin-induced hypoglycemia when the release of this hormone is suppressed during hypoglycemia-associated autonomic failure (5, 6), and by recent work showing that deletion of melanocortin 4 receptors from preganglionic sympathetic neurons leads to elevated levels of blood glucose (7).Given the involvement of the sympathetic nervous system in the CRR, modulation of autonomic activity is thus likely to alter the ability to respond to a hypoglycemic challenge. However, unlike in the CNS, where long-lasting changes in synaptic strength are known to be associated with functional consequences (8-10), whether the output ...

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Section: Discussionmentioning

confidence: 96%

mentioning

confidence: 99%

Fasting induces a form of autonomic synaptic plasticity that prevents hypoglycemia

Wang

Whim

2016

Proc. Natl. Acad. Sci. U.S.A.

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“…These observations prompted investigations into how sympathetic tone affects the production and release of leukocytes from BM [61]. Indeed, the sympathetic nervous system has recently emerged as a key component and regulator of the stem cell niche [62]. …”

Section: Role Of the Pns In The Development Deployment And Homeostamentioning

confidence: 99%

“…As we cannot expound on these topics in depth within the scope of this article, we provide below only a brief overview highlighting a few examples and otherwise refer the reader to recent reviews [62, 235]. …”

Section: Neuro-immune Interactions During Infection and Diseasementioning

confidence: 99%

The Regulation of Immunological Processes by Peripheral Neurons in Homeostasis and Disease

Ordovás-Montañés

Rakoff-Nahoum

Huang

et al. 2015

Trends in Immunology

149

123

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The nervous system and the immune system are the principal sensory interfaces between the internal and external environment. They are responsible for recognizing, integrating, and responding to varied stimuli, and have the capacity to form memories of these encounters leading to learned or ‘adaptive’ future responses. Here, we review the current understanding of the cross-regulation between these systems. The autonomic and somatosensory nervous systems regulate both the development and deployment of immune cells, with broad functions that impact hematopoiesis as well as priming, migration and cytokine production. In turn, specific immune cell subsets contribute to homeostatic neural circuits such as those controlling metabolism, hypertension and the inflammatory reflex. We examine the contribution of the somatosensory system to autoimmune, autoinflammatory, allergic, and infectious processes in barrier tissues and in this context, discuss opportunities for therapeutic manipulation of neuro-immune interactions.

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“…Interestingly, signals from the sympathetic nervous system regulate pericytes' function in the bone marrow microenvironment [29,30]. O'Farrell and colleagues showed that half of cardiac pericytes are located close to sympathetic neurons varicosities, implicating a possible role of noradrenergic regulation in pericytes' behavior [9].…”

Section: Perspectives/future Directionsmentioning

confidence: 99%

Pericytes constrict blood vessels after myocardial ischemia

Costa

Paiva

Andreotti

et al. 2018

Journal of Molecular and Cellular Cardiology

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No-reflow phenomenon is defined as the reduced blood flow after myocardial ischemia. If prolonged it leads to profound damages in the myocardium. The lack of a detailed knowledge about the cells mediating no-reflow restricts the design of effective therapies. Recently, O'Farrell et al. (2017) by using state-of-the-art technologies, including high-resolution confocal imaging in combination with myocardial ischemia/reperfusion mouse model, reveal that pericytes contribute to the no-reflow phenomenon post-ischemia in the heart. Strikingly, intravenous adenosine increased vascular diameter at pericyte site after cardiac ischemia. This study provides a novel therapeutic target to inhibit no-reflow phenomenon after myocardial ischemia.

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Neural Regulation of Hematopoiesis, Inflammation, and Cancer

Cited by 211 publications

References 153 publications

Fasting induces a form of autonomic synaptic plasticity that prevents hypoglycemia

Fasting induces a form of autonomic synaptic plasticity that prevents hypoglycemia

The Regulation of Immunological Processes by Peripheral Neurons in Homeostasis and Disease

Pericytes constrict blood vessels after myocardial ischemia

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