Interaction of Circulating Hormones With the Brain: The Roles of the Subfornical Organ and the Organum Vasculosum of the Lamina Terminalis

McKinley, Michael J.; Allen, Andrew M.; Burns, Peta; Colvill, L M; Oldfield, Brian J.

doi:10.1111/j.1440-1681.1998.tb02303.x

Cited by 139 publications

(105 citation statements)

References 38 publications

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“…Particularly pertinent to the heart failure syndrome are those PVN neurons that produce and release AVP and CRF (146) and those that project to the principal centers of sympathetic drive, the rostral ventrolateral medulla (RVLM) and the intermediolateral cell column (IML) of the spinal cord (148). PVN neurons receive and integrate ascending signals from the hindbrain regions related to pressure and volume within the cardiovascular system (107) and signals from forebrain regions including the circumventricular organs of the lamina terminalis, which lack a blood-brain barrier and thus sense the presence of blood-borne neuroactive peptides (108). Figure 1 illustrates this concept, showing that the discharge rate of a single PVN neuron is increased by blood-borne ANG I or ANG II administered into the ipsilateral carotid artery (ICA) but also by a reduction in arterial pressure induced by intravenous sodium nitroprusside.…”

Section: The Hypothalamus and Pvn In Heart Failurementioning

confidence: 99%

Heart failure and the brain: new perspectives

Felder¹,

Francis²,

Zhang³

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

110

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Heart failure and the brain: new perspectives. Am J Physiol Regul Integr Comp Physiol 284: R259-R276, 2003; 10.1152/ajpregu.00317.2002.-Despite recent therapeutic advances, the prognosis for patients with heart failure remains dismal. Unchecked neurohumoral excitation is a critical element in the progressive clinical deterioration associated with the heart failure syndrome, and its peripheral manifestations have become the principal targets for intervention. The link between peripheral systems activated in heart failure and the central nervous system as a source of neurohumoral drive has therefore come under close scrutiny. In this context, the forebrain and particularly the paraventricular nucleus of the hypothalamus have emerged as sites that sense humoral signals generated peripherally in response to the stresses of heart failure and contribute to the altered volume regulation and augmented sympathetic drive that characterize the heart failure syndrome. This brief review summarizes recent studies from our laboratory supporting the concept that the forebrain plays a critical role in the pathogenesis of ischemiainduced heart failure and suggesting that the forebrain contribution must be considered in designing therapeutic strategies. Forebrain signaling by neuroactive products of the renin-angiotensin system and the immune system are emphasized.angiotensin; aldosterone; cytokines; tumor necrosis factor; immune system; renin; vasopressin; sympathetic; extracellular fluid volume; baroreflex THE IMPORTANCE OF AUTONOMIC dysfunction to the progression of heart failure is firmly established (55,113,120,152). The most effective treatments for heart failure specifically target the peripheral manifestations of neurohumoral activation (86,113). Yet the understanding of the mechanisms leading to neurohumoral excitation in heart failure is still quite limited.Over the last several decades, substantial evidence has been amassed to support the concept that peripheral afferent systems innervating the heart and vascular tree are altered in heart failure. Dysfunction has been described in all components of the reflexes mediated by these cardiovascular afferent systems-the afferent fibers themselves, the central processing of the afferent signals, the efferent innervation of the end organs, and the end organs themselves. In general, the influence of low-and high-pressure baroreceptors (40,42,191) that normally restrain sympathetic drive and vasopressin release is diminished, whereas the excitatory influences of arterial chemoreceptors (161) and cardiac sympathetic afferent fibers (100) are enhanced.Central nervous system (CNS) neurons affecting cardiovascular regulation respond to humoral as well neural signals. Blood-borne neuroactive peptides, too large to readily cross the blood-brain barrier, may influence the brain by activating sensory neurons at specific sites in hindbrain and forebrain that lack a blood-brain barrier (15,18) or by inducing the release of mediators that do penetrate the barrier (135). These neuroactive s...

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Section: The Hypothalamus and Pvn In Heart Failurementioning

confidence: 99%

Heart failure and the brain: new perspectives

Felder¹,

Francis²,

Zhang³

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

110

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“…The SFO is a circumventricular organ structure that has essential actions in the integrative regulation of cardiovascular, immune, feeding, and reproductive function (McKinley et al, 1998;Cottrell and Ferguson, 2004). It is ideally situated in the forebrain to be exposed to both blood-borne signals and those circulating within the CNS.…”

Section: Introductionmentioning

confidence: 99%

Prokineticin 2 Modulates the Excitability of Subfornical Organ Neurons

Cottrell

Zhou²,

Ferguson³

2004

J. Neurosci.

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The recent discovery of prokineticin 2 (PK2) expression in the suprachiasmatic nucleus and its receptors in critical autonomic control centers of the brain, including the subfornical organ (SFO), suggests the intriguing possibility that PK2 regulates the excitability of SFO neurons and thus influences autonomic function. Using current-clamp techniques to record from dissociated SFO neurons, we examined the effects of PK2 on the excitability of these cells. PK2 (20 nM) induced depolarizations in 40% of SFO neurons (n ϭ 45; mean, 7.5 Ϯ 1.7 mV), an effect that was reversible, PK2-specific, and concentration dependent. The depolarization was accompanied by an increase in action potential frequency from 0.4 Ϯ 0.1 to 1.4 Ϯ 0.5 Hz in responding cells (n ϭ 10). This excitatory effect appears to be, in part, attributable to a PK2-induced decrease in the delayed rectifier potassium current (I K ). In 10 SFO neurons recorded using perforated patch voltage-clamp techniques, six demonstrated a reversible decrease in I K (mean decrease, 26.7 Ϯ 6.4%) in response to 20 nM PK2, whereas artificial CSF alone was without an effect on these currents. These data are the first to show excitatory effects of PK2 on neurons and, in addition, demonstrate that this peptide modulates voltage-activated K ϩ channels. The activation of SFO neurons by PK2 illustrates a mechanism through which this peptide may exert circadian control of autonomic functions.

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“…The SFO was found to contain neurons that expressed STC-1 immunoreactivity and contained both protein and gene expression for STC-1. The findings that STC-1 is produced within the SFO combined with the previous finding that SFO contains putative STC-1 receptors (45), suggests that STC-1 plays an important role in the function of neuronal systems controlling body fluid balance (7,15,36,37). In addition, as SFO neurons have been shown to contain STC-1 binding activity (45) and STC-1 is constitutively expressed within the SFO, this suggests that STC-1 may also function in an autocrine/paracrine manner (24,34) in SFO neuronal function (6,68,69).…”

Section: Discussionmentioning

confidence: 71%

“…The role of STC-1 within the SFO is not known, although it may function in modulating intracellular calcium concentrations within neurons, which could affect their excitability (17,(67)(68)(69). The SFO has been suggested to be one of the most important structures within the forebrain laminae terminalis in the regulation of electrolyte and body fluid homeostasis (1,3,7,12,13,25,31,36,37). Electrical and chemical stimulation of SFO has been reported to elicit dipsogenic responses in mammals (13,46).…”

mentioning

confidence: 99%

“…Immunohistochemical and autoradiographic binding studies have demonstrated that the SFO is a major site within the central nervous system at which the octapeptide ANG II binds within the central nervous system (22, 38) and activates neuronal circuits involved in the regulation of fluid and sodium balance, and blood pressure (12,13,15,25,36,37). ANG II AT 1 receptors (AT 1 R) have been identified on neurons throughout the SFO (44,47,56) and are known to mediate the dipsogenic and autonomic responses to ANG II (53, 54).…”

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confidence: 99%

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Stanniocalcin-1 in the subfornical organ inhibits the dipsogenic response to angiotensin II

Moreau

Iqbal

Turner

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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in the subfornical organ inhibits the dipsogenic response to angiotensin II. Am J Physiol Regul Integr Comp Physiol 303: R921-R928, 2012. First published August 29, 2012 doi:10.1152 doi:10. /ajpregu.00057.2012 for the calcium-regulating glycoprotein hormone stanniocalcin-1 (STC-1) have been found within subfornical organ (SFO), a central structure involved in the regulation of electrolyte and body fluid homeostasis. However, whether SFO neurons produce STC-1 and how STC-1 may function in fluid homeostasis are not known. Two series of experiments were done in Sprague-Dawley rats to investigate whether STC-1 is expressed within SFO and whether it exerts an effect on water intake. In the first series, experiments were done to determine whether STC-1 was expressed within cells in SFO using immunohistochemistry, and whether protein and gene expression for STC-1 existed in SFO using Western blot and quantitative RT-PCR, respectively. Cells containing STC-1 immunoreactivity were found throughout the rostrocaudal extent of SFO. STC-1 protein expression within SFO was confirmed with Western blot, and SFO was also found to express STC-1 mRNA. In the second series, microinjections (200 nl) of STC-1, ANG II, a combination of the two or the vehicle were made into SFO in conscious, unrestrained rats. Water intake was measured at 0700 for a 1-h period after each injection in animals. Microinjections of STC-1 (17.6 or 176 nM) alone had no effect on water intake compared with controls. However, STC-1 not only attenuated the drinking responses to ANG II for about 30 min, but also decreased the total water intake over the 1-h period. These data suggest that STC-1 within the SFO may act in a paracrine/autocrine manner to modulate the neuronal responses to blood-borne ANG II. These findings also provide the first direct evidence of a physiological role for STC-1 in central regulation of body fluid homeostasis. body fluid homeostasis; thirst; circumventricular organs; calciumregulating glycoprotein STANNIOCALCIN (STC) IS A GLYCOPROTEIN hormone first identified and characterized within bony fish corpuscles of Stannius, endocrine glands derived from renal tubular cells (18,24,29,63,64). These glands are thought to produce and release STC into the circulation in response to rising serum calcium levels (11,18,29,64). The STC then acts on the gills and gut epithelial cells to reduce calcium uptake, while STC within the kidney causes increases in reabsorption of phosphate (11,18,24), a mechanism that likely aids in chelating excess extracellular calcium (18,24). The net effect of these STC actions is the restoration of serum calcium levels (14,18,24,62).A mammalian homolog of STC has been identified that shares a 73% amino acid sequence homology with fish STC (41). Mammalian STC-1 is a disulfide-linked glycoprotein dimer of identical subunits (41), which is expressed in a variety of tissues, including heart, kidney, adipose tissue, skeletal muscle, lung, ovaries (18, 24), and brain (67-69). STC-1 functions in the cells of these tissues ...

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Interaction of Circulating Hormones With the Brain: The Roles of the Subfornical Organ and the Organum Vasculosum of the Lamina Terminalis

Cited by 139 publications

References 38 publications

Heart failure and the brain: new perspectives

Heart failure and the brain: new perspectives

Prokineticin 2 Modulates the Excitability of Subfornical Organ Neurons

Stanniocalcin-1 in the subfornical organ inhibits the dipsogenic response to angiotensin II

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