Microarray analysis of the transcriptome of the subfornical organ in the rat: regulation by fluid and food deprivation

Hindmarch, Charles; Fry, Mark; Yao, Song T.; Smith, Pauline; Murphy, David; Ferguson, Alastair V.

doi:10.1152/ajpregu.90560.2008

Cited by 63 publications

(68 citation statements)

References 57 publications

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“…25). These results confirm and extend recent findings of gene array studies from our laboratory, demonstrating the presence of leptin receptor mRNA in the SFO (20). In the present study, we sought to identify whether the mRNA was translated into a functional receptor using two approaches: 1) immunohistochemistry for the receptor and 2) leptin-induced activation of STAT3, revealed as nuclear labeling of pSTAT3 immunoreactivity.…”

Section: Discussionsupporting

confidence: 87%

See 1 more Smart Citation

The subfornical organ: a central nervous system site for actions of circulating leptin

Smith

Chambers²,

Price³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Adipose tissue plays a critical role in energy homeostasis, secreting adipokines that control feeding, thermogenesis, and neuroendocrine function. Leptin is the prototypic adipokine that acts centrally to signal long-term energy balance. While hypothalamic and brain stem nuclei are well-established sites of action of leptin, we tested the hypothesis that leptin signaling occurs in the subfornical organ (SFO). The SFO is a circumventricular organ (CVO) that lacks the normal blood-brain barrier, is an important site in central autonomic regulation, and has been suggested to have a role in modulating peripheral signals indicating energy status. We report here the presence of mRNA for the signaling form of the leptin receptor in SFO and leptin receptor localization by immunohistochemistry within this CVO. Central administration of leptin resulted in phosphorylation of STAT3 in neurons of SFO. Whole cell currentclamp recordings from dissociated SFO neurons demonstrated that leptin (10 nM) influenced the excitability of 64% (46/72) of SFO neurons. Leptin was found to depolarize the majority of responsive neurons with a mean change in membrane potential of 7.3 Ϯ 0.6 mV (39% of all SFO neurons), while the remaining cells that responded to leptin hyperpolarized (Ϫ6.9 Ϯ 0.7 mV, 25% of all SFO neurons). Similar depolarizing and hyperpolarizing effects of leptin were observed in recordings from acutely prepared SFO slice preparations. Leptin was found to influence the same population of SFO neurons influenced by amylin as three of four cells tested for the effects of bath application of both amylin and leptin depolarized to both peptides. These observations identify the SFO as a possible central nervous system location, with direct access to the peripheral circulation, at which leptin may act to influence hypothalamic control of energy homeostasis. circumventricular organ; hypothalamus ADIPOSE TISSUE PLAYS A CRITICAL role in energy homeostasis, secreting adipokines that control feeding, thermogenesis, immunity, and neuroendocrine function. Leptin, a 16 kDa peptide, is the prototypic adipokine that has been shown to be an important afferent signal regulating body weight. A missense mutation in the ob gene (the gene that encodes leptin) in the ob/ob mouse, results in a markedly obese phenotype that is normalized by both systemic and central leptin administration (9,19,37). Leptin administration also has been shown to dose-dependently decrease body weight, preferentially reducing body fat while sparing lean tissue in both ob/ob and wild-type mice (18,19). Plasma leptin levels reflect both energy stores and acute energy balance. Circulating leptin decreases food intake and increases energy expenditure through activation of receptors in hypothalamic and brain stem neurons (16) .The leptin receptor, encoded by the Ob-R gene, was isolated from choroid plexus by expression cloning and is a member of the cytokine family (48). Although five leptin receptor isoforms have been identified (Ob-Ra to Ob-Re), only the long form of the rece...

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Section: Discussionsupporting

confidence: 87%

“…In addition, recent gene array studies from our own laboratory have revealed the presence of the leptin receptor mRNA in the SFO (20). The present study was undertaken to test the hypothesis that leptin signaling occurs in the SFO.…”

mentioning

confidence: 97%

The subfornical organ: a central nervous system site for actions of circulating leptin

Smith

Chambers²,

Price³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Studies show that various physical stress procedures such as water and food deprivation, exposure to cold, hypotension, hypertonic extracellular volume expansion, lipopolysaccharide treatment regulate CART expression in the brain [48][49][50][51][52] . Studies demonstrate that psychological stress also changes CART peptide and mRNA expression in the hypothalamus, limbic areas, brainstem and the adrenal gland.…”

Section: Cart and Stressmentioning

confidence: 99%

Cocaine- and amphetamine-regulated transcript (CART): A possible regulator of the stress response

Balkan¹

2013

OA Neurosciences

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Introduction Cocaine-and amphetamine-regulated transcript peptides have been implicated in the endocrine and autonomic regulation, food intake and anxiety. Anatomical studies demonstrate that cocaine-and amphetamine-regulated transcript mRNA and peptides are expressed intensely in the hypothalamo-pituitary-adrenal gland axis and sympatho-adrenal system. In parallel with the anatomical studies, functional studies show that cocaine-and amphetamine-regulated transcript peptides increase the activity of the hypothalamo-pituitary-adrenal axis and sympatho-adrenal system. Also, various stress procedures regulate cocaine-and amphetamine-regulated transcript peptide and mRNA expression in the frontal cortex, amygdala, hypothalamus and adrenal gland. Based on these data, this review discusses the possible role of cocaineand amphetamine-regulated transcript peptides in the regulation of the stress response. ConclusionThere is substantial literature which shows that cocaine-and amphetamineregulated transcript has significant effects on the hypothalamo-pituitaryadrenal axis and sympatho-adrenal system activity. Although increasing number of studies report that cocaine-and amphetamine-regulated transcript expression is regulated by the stress response, the exact role of

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“…The AP is probably not unique in this regard because the SFO also has a similar assortment of diverse channels and peptide receptors (16). The OVLT has not yet been analyzed in this manner.…”

mentioning

confidence: 99%

“…The gene chip studies have added a great amount of information to our understanding of the CVOs, but they have implicitly assumed that the CVOs are homogenous structures (16,17), and clearly, this is not the case. Each CVO has its own defined cytoarchitectonic regions and contains a heterogeneous group of neurons (24).…”

mentioning

confidence: 99%

5-HT neurons of the area postrema become c-Fos-activated after increases in plasma sodium levels and transmit interoceptive information to the nucleus accumbens

Miller

Loewy

2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Miller RL, Loewy AD. 5-HT neurons of the area postrema become c-Fos-activated after increases in plasma sodium levels and transmit interoceptive information to the nucleus accumbens. Am J Physiol Regul Integr Comp Physiol 306: R663-R673, 2014. First published March 5, 2014 doi:10.1152/ajpregu.00563.2013 neurons of the area postrema (AP) represent one neuronal phenotype implicated in the regulation of salt appetite. Tryptophan hydroxylase (Tryp-OH, synthetic enzyme-producing 5-HT) immunoreactive neurons in the AP of rats become c-Fos-activated following conditions in which plasma sodium levels are elevated; these include intraperitoneal injections of hypertonic saline and sodium repletion. Non-Tryp-OH neurons also became c-Fos-activated. Sodium depletion, which induced an increase in plasma osmolality but caused no significant change in the plasma sodium concentration, had no effect on the c-Fos activity in the AP. Epithelial sodium channels are expressed in the Tryp-OH-immunoreactive AP neurons, possibly functioning in the detection of changes in plasma sodium levels. Since little is known about the neural circuitry of these neurons, we tested whether the AP contributes to a central pathway that innervates the reward center of the brain. Stereotaxic injections of pseudorabies virus were made in the nucleus accumbens (NAc), and after 4 days, this viral tracer produced retrograde transneuronal labeling in the Tryp-OH and non-Tryp-OH AP neurons. Both sets of neurons innervate the NAc via a multisynaptic pathway. Besides sensory information regarding plasma sodium levels, the AP¡NAc pathway may also transmit other types of chemosensory information, such as those related to metabolic functions, food intake, and immune system to the subcortical structures of the reward system. Because these subcortical regions ultimately project to the medial prefrontal cortex, different types of chemical signals from visceral systems may influence affective functions. area postrema; circumventricular organs; epithelial sodium channels; nucleus accumbens; ventral tegmental area THE AREA POSTREMA (AP) IS a sensory circumventricular organ (CVO) located in the dorsal midline of the medulla oblongata, which protrudes into the 4th ventricle. Its terminal arterial supply is made up of fenestrated capillaries with pores measuring ϳ60 -80 nm, which allow the passage of solutes and small peptides from the plasma into the AP, so the local neurons and glial cells are bathed in a similar chemical environment as the plasma. CVO neurons detect small changes in the plasma concentration of many of these chemicals and convert this information into neural activity that is sent via feed-forward excitatory pathways to homeostatic regulatory sites in the hypothalamus. For example, the forebrain CVO neurons, originating in the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), project to the vasopressin and oxytocin neurons of the supraoptic and paraventricular hypothalamic nuclei and elicit the release of these hormones that...

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Microarray analysis of the transcriptome of the subfornical organ in the rat: regulation by fluid and food deprivation

Cited by 63 publications

References 57 publications

The subfornical organ: a central nervous system site for actions of circulating leptin

The subfornical organ: a central nervous system site for actions of circulating leptin

Cocaine- and amphetamine-regulated transcript (CART): A possible regulator of the stress response

5-HT neurons of the area postrema become c-Fos-activated after increases in plasma sodium levels and transmit interoceptive information to the nucleus accumbens

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