Sensory circumventricular organs: central roles in integrated autonomic regulation

Cottrell, G. Trevor; Ferguson, Alastair V.

doi:10.1016/j.regpep.2003.09.004

Cited by 184 publications

(140 citation statements)

References 170 publications

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“…AP neurons are responsive to a number of circulating peptide hormones, including those involved in energy homeostasis, such as cholecystokinin, orexin-A, amylin, and ghrelin, and those involved in the regulation of blood pressure, such as atrial natriuretic peptide, angio-tensin, and vasopressin (McKinley et al, 2003;Cottrell and Ferguson, 2004). AP neurons integrate hormonal and neural signals and project to centers involved in homeostatic control, including nucleus of the solitary tract, rostral ventrolateral medulla, lateral parabrachial nucleus, and lateral hypothalamus (Ferguson, 1991;Bishop and Hay, 1993;McKinley et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Area Postrema Neurons Are Modulated by the Adipocyte Hormone Adiponectin

Fry¹,

Smith²,

Hoyda³

et al. 2006

J. Neurosci.

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Adiponectin is an adipocyte-derived peptide hormone involved in energy homeostasis and the pathogenesis of obesity, including hypertension. Area postrema (AP) lacks a blood-brain barrier and is a critical homeostatic integration center for humoral and neural signals. Here we investigate the role of AP in adiponectin signaling. We show that rat AP expresses AdipoR1 and AdipoR2 adiponectin receptor mRNA. We used current-clamp electrophysiology to investigate whether adiponectin influenced membrane properties of AP neurons and found that ϳ60% of rat AP neurons tested were sensitive to adiponectin. Additional electrophysiology experiments coupled with single-cell reverse transcription-PCR indicated that all neurons that expressed both subtypes of receptor were sensitive to adiponectin, whereas neurons expressing only one subtype were predominantly insensitive. Last, microinjection of adiponectin into AP caused significant increases in arterial blood pressure, with no change in heart rate, suggesting that adiponectin acts at AP to provide a possible link between control of energy homeostasis and cardiovascular function.

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Section: Introductionmentioning

confidence: 99%

Area Postrema Neurons Are Modulated by the Adipocyte Hormone Adiponectin

Fry¹,

Smith²,

Hoyda³

et al. 2006

J. Neurosci.

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“…Circumventricular organs of the brain, such as the median eminence of the hypothalamus, offer such a model because they contain an abundance of glial-endothelial contacts amenable to experimental scrutiny. Circumventricular organs are capable of sensing information reaching the brain via the bloodstream and, conversely, conveying information from the brain to the periphery via the release of neurohormones into the circulation (Cottrell and Ferguson, 2004). In addition to astroglial cells, circumventricular organs are endowed with modified ependymoglial cells (Palkovitz, 1987).…”

Section: Introductionmentioning

confidence: 99%

Vascular Endothelial Cells Promote Acute Plasticity in Ependymoglial Cells of the Neuroendocrine Brain

et al. 2004

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Glial and endothelial cells interact throughout the brain to define specific functional domains. Whether endothelial cells convey signals to glia in the mature brain is unknown but is amenable to examination in circumventricular organs. Here we report that purified endothelial cells of one of these organs, the median eminence of the hypothalamus, induce acute actin cytoskeleton remodeling in isolated ependymoglial cells and show that this plasticity is mediated by nitric oxide (NO), a diffusible factor. We found that both soluble guanylyl cyclase and cyclooxygenase products are involved in this endothelial-mediated control of ependymoglia cytoarchitecture. We also demonstrate by electron microscopy that activation of endogenous NO release in the median eminence induces rapid structural changes, allowing a direct access of neurosecretory axons containing gonadotropin-releasing hormone (GnRH) (the neuropeptide controlling reproductive function) to the portal vasculature. Local in vivo inhibition of NO synthesis disrupts reproductive cyclicity, a process that requires a pulsatile, coordinated delivery of GnRH into the hypothalamic-adenohypophyseal portal system. Our results identify a previously unknown function for endothelial cells in inducing neuroglial plasticity and raise the intriguing possibility that endothelial cells throughout the brain may use a similar signaling mechanism to regulate glial-neuronal interactions.

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“…13 These are small regions of the brain that do not have the normal structure of the blood-brain barrier and therefore lie 'outside' of the brain in terms of their ability to respond to circulating factors present in the blood stream. 27 In a series of elegant studies they show the capacity of the subfornical organ and the area postrema, two important CVOs, to respond to both gut peptides and the adipocytokine adiponectin. 13 The CVOs express a huge range of receptors for peptides, whose physicochemical properties prevent them from accessing other regions of the brain directly.…”

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confidence: 99%

“…13 The CVOs express a huge range of receptors for peptides, whose physicochemical properties prevent them from accessing other regions of the brain directly. 27 They also possess receptors for ion channels, steroids, lipid mediators and other substances and have extensive projections to brain regions involved in energy homeostasis and so are wellpositioned to respond to circulating factors and initiate Peripheral satiety signals KA Sharkey S4 …”

mentioning

confidence: 99%

“…27 They also possess receptors for ion channels, steroids, lipid mediators and other substances and have extensive projections to brain regions involved in energy homeostasis and so are wellpositioned to respond to circulating factors and initiate appropriate central responses. 27 Timofeeva and colleagues 28 recently illustrated how CVOs might participate in feeding responses. They measured the activation of brain regions in response to refeeding after a fast, using the expression of c-fos as a marker of neuronal activation.…”

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confidence: 99%

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Peripheral satiety signals: view from the Chair

Sharkey

2009

Int J Obes

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The discovery and characterization of peripheral signals that regulate food intake and energy balance dates back over 50 years. Beginning with the 'glucostatic' and 'lipostatic' hypotheses, nutrients were considered strong candidates that could 'tell' the brain the state of satiety (glucose) or overall energy stores (fat), so that food intake and energy expenditure could be regulated to maintain energy balance. 1,2 Both of these hypotheses endure to this day. The lipostatic hypothesis remains as a central concept in our understanding of the regulation of energy balance. This is based on the key observations that (a) insulin is secreted from the pancreas in direct proportion to fat stores and provides a signal to the brain to initiate long-term changes in energy expenditure and food intake 3 and (b) the peptide hormone leptin is released from adipose tissue itself, and defects in either the production or the signalling of leptin lead to obesity. 4 The glucostatic hypothesis received validation with the discovery of glucose-sensitive neurons in the hypothalamic regions involved in the control of energy balance. 5,6 Over the years, other nutrient-based hypotheses were developed and the existing ones were modified, but none of these were completely capable of explaining the shortterm control of food intake or certain aspects of long-term energy balance. In the early 1970s, Gibbs et al. 7 found a gastrointestinal hormone, cholecystokinin (CCK), that produced satiety in rats. This discovery heralded the era of the 'gut hormones' as regulators of both food intake and energy balance. We now recognize more than 20 gut-derived peptides and lipid mediators are involved in aspects of energy homeostasis. [8][9][10] Many of these have now been tested or developed as potential therapeutic agents for the treatment of metabolic disorders or to aid in weight management. It seems unlikely that the full complement of peripheral energy balance signals have been discovered. As more are found, the opportunities for the development of novel therapeutics must be balanced with challenges of understanding their role in the physiology and pathophysiology of this complex regulatory system. Major challenges remain: How do the plethora of peripheral signals get integrated in the brain? Similarly, how does the brain actually receive these signals in the first place? In the three articles following this viewpoint, Timothy Moran, 11 Harvey Grill, 12 and Alastair Ferguson 13 and their colleagues begin to address these challenges by outlining where signals released from the gut and adipose tissues act to regulate energy balance.Peripheral signals arising from the gut are key elements in food intake regulation and energy balance, as discussed by Timothy Moran. 11 He illustrates how enteroendocrine peptides are released in sequence along the length of the gut and across the duration of a meal. These peptides regulate both the initiation of a meal and its termination. There are a multitude of anorexigenic peptide signals released from the gut. Moran ...

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Sensory circumventricular organs: central roles in integrated autonomic regulation

Cited by 184 publications

References 170 publications

Area Postrema Neurons Are Modulated by the Adipocyte Hormone Adiponectin

Area Postrema Neurons Are Modulated by the Adipocyte Hormone Adiponectin

Vascular Endothelial Cells Promote Acute Plasticity in Ependymoglial Cells of the Neuroendocrine Brain

Peripheral satiety signals: view from the Chair

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