Subfornical Organ


Receptors and synthesizing and degrading enzymes for ECs were widely distributed in rat ependyma and subependyma, marginal glia, and circumventricular organs (CVOs) such as the choroid plexus, subfornical organ, subcommissural organ, median eminence, and area postrema.  

Neuronal activity as assessed by Fra-like immunoreactivity increased transiently in the subfornical organ (SFO), but progressively in the paraventricular (PVN) and supraoptic (SON) nuclei.  

The subfornical organ, belongs to a group of specialized central nervous system structures, the cirumventricular organs, that are characterized by the lack of the normal blood brain barrier, such that circulating lipophobic substances may act on neurons within this region, and via well documented efferent neural projections to hypothalamic autonomic control centers, influence autonomic function. This review focuses on the role of the subfornical organ in sensing peripheral signals and transmitting this information to autonomic control centers in the hypothalamus..  

In the supraoptic nucleus, paraventricular nucleus, and subfornical organ, Na(+)-rich aCSF did not affect mRNA expression levels of the studied genes.  

These regions contain a subset of serotonergic neurons that projects via the dorsal raphe periventricular tract to periventricular structures, including the subfornical organ and ependymal layer, and to the ventricular system.  

Ang II-induced c-fos expression was detected in the paraventricular nuclei, median preoptic nuclei, supraoptic nuclei, and subfornical organ in the brain, in association with reduced forebrain AT(2) receptor protein abundance in the offspring prenatally exposed to hypoxia.  

subfornical organ and central amygdala, as revealed by immediate early gene c-Fos immunoreactivity or focal lesions.  

In the present study, we revealed that icv administered relaxin-3 induced dense Fos-like immunoreactivity (Fos-LI) in the rat hypothalamus and circumventricular organs including the organum vasculosum of the lamina terminalis, the median preoptic nucleus, supraoptic nucleus (SON), the subfornical organ (SFO) and the paraventricular nucleus (PVN), that are related to the central regulation of body fluid balance.  

The subfornical organ (SFO) is a CVO that has been implicated in the regulation of energy balance as a consequence of the ability of SFO neurons to respond to a number of different circulating satiety signals including amylin, CCK, PYY and ghrelin.  

After WD-PR, the Fos-Ir persisted elevated in the lamina terminalis of all strains, but notably in the subfornical organ of the SHR.  

In this immunohistochemical study of rat brain, AQP1 has also been found in microvessel endothelia, probably of the fenestrated type, in all circumventricular organs (except the subcommissural organ and the vascular organ of the lamina terminalis): in the median eminence, pineal, subfornical organ, area postrema and choroid plexus. In the subfornical organ and area postrema in which many, but not all, microvessels are fenestrated, not all microvessels are AQP1-immunoreactive.  

Also, there was no significant difference in the activity of subfornical organ neurons projecting to the SON between the two genotypes when stimulated by water deprivation.  

Analysis of c-fos mRNA expression in the median preoptic nucleus and subfornical organ in response to either WD or SL showed attenuated expression in APJ(-/-) compared to wild-type mice.  

The primary objective of the present study was to investigate the potential role of two circumventricular organs (CVOs), the area postrema (AP) and the subfornical organ (SFO), in mediating the metabolic and CNS-stimulating effects of Ex-4.  

Electrical stimulation (200 microA) of satiated animals with subfornical organ (SFO) electrode placement (n=6) elicited feeding in all animals tested with a mean latency to eat of 8.0+/-4.0 min after termination of SFO stimulation (mean food consumption: 0.6+/-0.12 g/100g bw).  

The lamina terminalis (LT) consists of the organum vasculosum of the LT (OVLT), the median preoptic nucleus (MnPO) and the subfornical organ (SFO).  

Regulation of Sirt1 mRNA levels in the subfornical organ (SFO) and in the substancia nigra part compacta (SNC) depended on gender.  

AT(1) receptor expression was increased in the subfornical organ and periventricular nucleus of the hypothalamus, but not in other brain regions measured.  

Intracerebroventricular somatostatin increased SON oxytocin and vasopressin neurone firing-rates, and increased Fos expression in the SON and paraventricular nucleus and in the subfornical organ.  

Cardiovascular and behavioral responses to circulating angiotensin require intact connectivity along the upper lamina terminalis joining the subfornical organ (SFO) with the median preoptic nucleus (MnPO).  

In the LPS group, iNOS mRNA expression was observed in the subfornical organ, but not in the paraventricular nucleus.  

In c-fos-mRFP1 transgenic rats, 90 min after hypertonic saline ip administration, nuclear mRFP1 fluorescence was observed abundantly in brain regions known to be osmosensitive, namely the median preoptic nucleus, organum vasculosum lamina terminalis, supraoptic nucleus, paraventricular nucleus, and subfornical organ.  

Recently we established that NADPH oxidase (Nox)-derived superoxide acting in the forebrain subfornical organ is critical in the physiological responses to central Ang-II. To dissect out the functional importance and unique roles of these Nox enzymes in the pressor and dipsogenic effects of central Ang-II, we developed adenoviral vectors expressing small interfering RNA to selectively silence Nox2 or Nox4 expression in the subfornical organ.  

We have shown previously that the chronic hypotensive effect of the angiotensin II AT1 receptor antagonist losartan is mediated, in part, by the subfornical organ (SFO).  

The subfornical organ (SFO) and the area postrema (AP), two of the sensory circumventricular organs (CVO), are known to play a role in the chronic central control of blood pressure.  

Released interleukin-1beta (IL-1beta) reaching cerebroventricles stimulates circumventricular organs (CVOs; subfornical organ, SFO; organum vasculosum lamina terminalis, OVLT), the median preoptic nucleus (MePO), and magnocellular and parvocellular neurons in the supraoptic (SON) and paraventricular (PVN) nuclei.  

The present study tested the hypotheses that 1) nitric oxide (NO) is involved in attenuated responses to ANG II in female mice, and 2) there is differential expression of neuronal NO synthase (nNOS) in the subfornical organ (SFO) and paraventricular nucleus (PVN) in response to systemic infusions of ANG II in males vs.  

Results showed that the Fos immunoreactivity (Fos-ir) expression in forebrain areas such as subfornical organ (SFO), paraventricular hypothalamic nuclei (PVN), supraoptic nucleus (SON) and organum vasculosum laminae terminalis (OVLT) all increased significantly and that the levels of ANG I, ANG II and ALD also increased in plasma and forebrain in rats fed with low sodium diet.  

We suggest that water deprivation causes changes of the classical ependyma and the specialized ependyma that differentiates into the SCO as well as other cirumventricular organs such as the subfornical organ and the organum vasculosum laminae terminalis known to control drinking behaviors..  

The median preoptic nucleus (MnPO) is densely innervated by efferent projections from the subfornical organ (SFO) and, therefore, is an important relay for the peripheral chemosensory and humoral information (osmolality and serum levels ANG II).  

Analysis of c-fos (Fos as given in MGI Database) mRNA expression in response to dehydration showed attenuation of expression within the subfornical organ, accentuated expression in the paraventricular nucleus, but no differences in expression in the supraoptic nucleus nor median pre-optic nucleus in APJ(-/-) mice compared with wild-type.  

Outside of the hypothalamus, a small number of kisspeptin fibres were identified in the bed nucleus of the stria terminalis, subfornical organ, medial amygdala, paraventricular thalamus, periaqueductal grey and locus coerulus.  

In marked contrast, RVLM injection of l-glutamate or gamma-aminobutyric acid produced exaggerated sympathetic nerve activity and arterial blood pressure responses in animals drinking 0.9% NaCl versus water after an acute ventral LT lesion or chronic lesion of the subfornical organ.  

Plasma angiotensin II may directly activate CNS pathways through the subfornical organ and chronically enhance activity by way of a neuromodulatory system.  

SFO, subfornical organ.  

Specifically, we review a developing literature that shows receptors for, and functional actions of, gastrointestinal hormones such as amylin, cholecystokinin, ghrelin and peptide YY in the area postrema and subfornical organ.  

The following review will focus on work identifying the subfornical organ (SFO), and its efferent projections to the paraventricular nucleus of the hypothalamus (PVN), as a critical component of the CNS circuitry activated by circulating angiotensin II.  

Using molecular and immunochemical approaches, we examined expression of the AT(1)R and phosphorylated MAPK in the paraventricular nucleus of the hypothalamus (PVN) and the subfornical organ (SFO) of rats receiving a chronic (4-wk) subcutaneous infusion of ANG II (0.6 microg/h) or saline (vehicle control), with or without concomitant (4-wk) intracerebroventricular (ICV) infusions of MAPK inhibitors or the AT(1)R blocker losartan.  

Ninety minutes, 5 h, and 24 h after liver reperfusion, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), interleukin 1alpha (IL-1alpha), and tumor necrosis factor alpha (TNFalpha) serum levels were analyzed and Fos-immunolabeled cells counted in subfornical organ (SFO), suprachiasmatic (SCH), paraventricular (PVN), supraoptic (SON), arcuate (ARC), and ventromedial (VMN) hypothalamic nuclei, locus coeruleus (LC), nucleus of the solitary tract (NTS), and A1/C1 catecholaminergic cell groups.  

ET(A)R activation at the subfornical organ (SFO) increases mean arterial pressure and renal sympathetic nerve activity (RSNA) as well as AVP secretion in awake rats.  

The present study was designed to investigate the effect of administration of adrenomedullin (ADM) into subfornical organ (SFO) on renal tubular Na(+),K(+)-ATPase activity in rats.  

AT(2) receptor blockade increased AT(1) receptor binding and mRNA expression not only in the subfornical organ and the median eminence, situated outside the blood brain barrier, but also in the hypothalamic paraventricular nucleus, located inside the blood brain barrier.  

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).  

Associated with the swallowing activation, c-fos immunoreactivity in the putative dipsogenic center, subfornical organ, was enhanced significantly.  

The results demonstrate marked MI-induced increases in superoxide radical formation in one of these forebrain regions, the subfornical organ (SFO).  

Five general brain regions contained retrogradely labeled neurons: cerebral cortex (infralimbic and insular regions), rostral forebrain structures (subfornical organ, organum vasculosum of the lamina terminalis, taenia tecta, nucleus accumbens, lateral septum, endopiriform nucleus, dorsal BST, substantia innominata, and, most prominently the amygdala--primarily its basomedial and central subnuclei), thalamus (central medial, intermediodorsal, reuniens, and, most prominently the paraventricular thalamic nucleus), hypothalamus (medial preoptic area, perifornical, arcuate, dorsomedial, parasubthalamic, and posterior hypothalamic nuclei), and brainstem (periaqueductal gray matter, dorsal and central superior raphe nuclei, parabrachial nucleus, pre-locus coeruleus region, NTS, and A1 noradrenergic neurons in the caudal ventrolateral medulla).  

In the brain of VDR-null mice, expression of c-Fos, which is known to associate with increased water intake, was increased in the hypothalamic paraventricular nucleus and the subfornical organ.  

We have employed microarray technology using Affymetrix 230 2.0 genome chips to initially catalog the transcriptome of the subfornical organ (SFO) under control conditions and to also evaluate the changes (common and differential) in gene expression induced by the challenges of fluid and food deprivation.  

This study was undertaken to test the hypothesis that the subfornical organ (SFO), a forebrain circumventricular structure, may also modulate the baroreflex.  

AT(1)-R protein, AT(1)-R mRNA, and AT(1)-R immunoreactivity increased in the paraventricular nucleus of hypothalamus and the subfornical organ of rats with ischemia-induced HF compared with sham-operated controls. Phosphorylated p44/42 MAPK, c-Jun N-terminal kinase, and p38 MAPK also increased in paraventricular nucleus and subfornical organ. A 4-week ICV infusion of the p44/42 MAPK inhibitor PD98059 or the c-Jun N-terminal kinase inhibitor SP600125 significantly decreased AT(1)-R protein and AT(1)-R immunoreactivity in the paraventricular nucleus and subfornical organ, but the p38 MAPK inhibitor SB203580 did not. In untreated HF rats 4 weeks after coronary ligation, a 3-hour ICV infusion of PD98059, SP600125, or losartan reduced AT(1)-R mRNA in paraventricular nucleus and subfornical organ.  

Several lines of evidence implicate the median preoptic nucleus (MnPO) as a downstream site of activation following binding of angiotensin II (ANG II) at the subfornical organ and organum vasculosum of the lamina terminalis.  

We investigated the influence of voltage-dependent calcium channels and nitric oxide (NO) on angiotensin II (ANG II)-pressor effect injected into subfornical organ (SFO).  

Pax2 expression was detected in the septum of the basal forebrain, hypothalamus, eminentia thalami and in the subfornical organ.  

The subfornical organ (SFO) and the organum vasculosum of the lamina terminalis (OVLT) are circumventricular organs that express AT1Rs that bind blood-borne ANGII and stimulate integrative and effector regions of the brain.  

Orexins did not attenuate the properties of excitatory (n=4) or inhibitory (n=7) postsynaptic currents evoked by subfornical organ stimulation.  

The subfornical organ (SFO), which is related to drinking and cardiovascular regulation, is activated by central application of nicotine (NIC) and angiotensin II (ANG).  

We have previously reported PK2 actions on subfornical organ (SFO) neurons, identifying this circumventricular organ as a target at which PK2 acts to influence autonomic control (Cottrell GT, and Ferguson AV.  

In subfornical organ slices, the application of ANG II resulted in a 21.5 +/- 2.5% increase in ROS production.  

Very high to high binding is also seen in brain regions associated with cardiovascular regulation (subfornical organ, median, medial and anteroventral preoptic nucleus, paraventricular nucleus of the hypothalamus, solitary tract nucleus), areas that harbor high densities of the AT1 Ang II receptor subtype.  

Balloon inflation over a 3 h period following Furo-Cap treatment decreased Fos-ir in the organum vasculosum of the lamina terminalis and the subfornical organ and increased Fos-ir in the lateral parabrachial nucleus and caudal ventrolateral medulla.  

Additionally, neurons of the organum vasculosum of the lamina terminalis, the dorsal and ventral components of the median preoptic nucleus and the rostral aspects of the subfornical organ exhibited dense STC-1 cytoplasmic staining.  

It is unclear which nicotinic acetylcholine receptor (nAChR) subtypes are involved in the nicotinic activation of cells in the subfornical organ (SFO).  

CONCLUSIONS: This review highlights data showing that individual afferent inputs (subfornical organ), signaling molecules (orexins, adiponectin), and interneurons (glutamate/GABA), all have the potential to influence (and thus coordinate) multiple PVN output pathways.  

Intracerebroventricular injections of angiotensin II (ANG) and nicotine activate the subfornical organ (SFO), an essential central nucleus for ANG-induced drinking.  

Some circulating peptides, such as angiotensin II, atrial natriuretic peptide and relaxin, influence central neural pathways subserving cardiovascular and body fluid homeostasis by acting on neurons in the subfornical organ, organum vasculosum of the lamina terminalis and area postrema, all of which lack a blood-brain barrier.  

Our previous studies showed that TTF-1 plays an important role in water homeostasis in the subfornical organ of rats and is involved in cerebrospinal fluid formation by regulation of aquaporin-1 transcription in the choroid plexus.  

The IL-6, which appeared in the blood after injection of MALP-2 into the air pouch was sufficient to cause a direct activation of brain cells in areas which lack a complete blood-brain barrier, namely in the sensory circumventricular organs (sCVOs), the organum vasculosum laminae terminalis (OVLT), the subfornical organ (SFO), and the area postrema (AP).  

Galanin inhibits electrical activation of angiotensin II-sensitive neurons in the subfornical organ, which is related to angiotensin II-induced drinking behavior and pressor responses.  

Osmoregulatory regions of the brain [ hypothalamic paraventricular and supraoptic nuclei, median preoptic nucleus, organum vasculosum of the lamina terminalis (OVLT), and subfornical organ] showed an increased number of neurons exhibiting Fos-immunoreactivity in response to intraperitoneal hypertonic NaCl in both Agt-/- mice and WT mice. Polyethylene glycol treatment increased Fos-immunoreactivity in the subfornical organ, OVLT, and supraoptic nuclei in WT mice but only increased Fos-immunoreactivity in the supraoptic nucleus in Agt-/- mice.  

The injections increased the numbers of c-Fos immunoreactive cells in the subfornical organ, median nucleus of preoptic area, organum vasculosum of lamina terminalis, paraventricular nucleus and supraoptic nucleus. Electrophysiological experiments using slice preparations and whole cell recordings showed that pilocarpine depolarized the membrane of neurons in the subfornical organ and suppressed the inhibitory GABAergic synaptic currents by a presynaptic action.  

As the subfornical organ (SFO) plays an important role in drinking behavior, hypocretins may excite SFO neurons.  

It is morphologically demonstrated that the subfornical organ (SFO) projects to the paraventricular hypothalamic nucleus (PVN) and also projects to the nucleus preopticus medianus (POMe), a relay nucleus of indirect projections from the SFO to PVN.  

In vivo, Ad-hACE2-eGFP infection (2x10(6) plaque-forming units intracerebroventricularly) produced time-dependent expression and activity (with a peak at 7 days) in the mouse subfornical organ. Furthermore, subfornical organ-targeted ACE2 overexpression dramatically reduced the Ang II-mediated drinking response. These data suggest that ACE2 overexpression in the subfornical organ impairs Ang II-mediated pressor and drinking responses at least by inhibiting the Ang II type 1 receptor expression.  

For instance, the paraventricular thalamic nucleus, the bed nucleus of the stria terminalis and the subfornical organ were highly labelled, as were the periaqueductal gray and the nucleus of the solitary tract.  

Rats injected with CTb in the dorsal midline of the thalamus and challenged with hypertonic saline had increased numbers of Fos/CTb double-positive neurons within the organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus, and insular cortex but not the subfornical organ.  

Following viral gene transfer of NF-kappaB-driven luciferase reporter to the subfornical organ (SFO), BLI enabled daily measurements of baseline TF activity in the same animal for 1 mo.  

The anorectic and dipsogenic effects of the pancreatic hormone amylin are mediated by the area postrema and the subfornical organ. We tested the effectiveness of a new amylin antagonist, a so-called RNA Spiegelmer, by electrophysiological in-vitro recordings from the rat subfornical organ and by immunohistological c-Fos studies in the area postrema. Amylin's excitatory effect on subfornical organ neurons was blocked by the anti-amylin Spiegelmer.  

Whereas the presence of [ 125I]pPYY(3-36)-related labeling was detected in the area postrema, subfornical organ, and median eminence.  

Fos-ir activity was quantified in the paraventricular nucleus (PVN), subfornical organ (SFO), supraoptic nucleus (SON), nucleus accumbens (NAc) shell and core, basolateral (BLA) and central amygdala (CeA), and medial prefrontal cortex (mPFC).  

Previous work has demonstrated that subfornical organ neurons exhibit spontaneous action potentials interspersed with periods of membrane potential oscillation.  

Results The slow down of weight-gaining, rise of serum corticosterone level, occurrence of psychological behavioral manifestations of unpeaceful restlessness such as exploring and attacking, enhance of c-Fos expression in the subfornical organ (SFO), median preoptic nucleus (MnPO), area postrema (AP), hypothalamic paraventricular nucleus (PVN), supraoptic nucleus (SON), medial (MeA) and central (CeA) amygdaloid nucleus and ventrolateral septum (LSV) were noticed in both EB and WR groups, except the nucleus of solitary tract (NTS) in which the Fos expression was decreased.  

The objective of this study was to analyze the proteins in the cerebrospinal fluid of spontaneously hypertensive rats and to study their possible role in the relationship between hydrocephalus, arterial hypertension and variations in the subfornical organ. Cerebrospinal fluid and extract of subfornical organ were processed by protein electrophoresis. Antisera against protein bands of 141, 117 and 48 kDa and Concanavalin A were used for immunohistochemical and western blot study of the subfornical organ, adjacent circumventricular structures and cerebrospinal fluid. The subfornical organ, third ventricle ependyma and choroideus plexus showed immunoreactive material for antibodies against 141kDa, 117 and 48 kDa proteins band (anti-B1, anti-B2 and anti-B3). The larger amount of the immunoreactive material was found in the subfornical organ of the spontaneously hypertensive rat. Our results and the alterations observed by other authors in the subfornical organ in hydrocephalic and hypertensive rats support the possibility that this circumventricular organ, some proteins of the cerebrospinal fluid and ventricular dilation could be connected with the physiopathology of this type of hypertension..  

The circumventricular organs are small sized structures lining the cavity of the third ventricle (neurohypophysis, vascular organ of the lamina terminalis, subfornical organ, pineal gland and subcommissural organ) and of the fourth ventricle (area postrema). Their particular location in relation to the ventricular cavities is to be noted: the subfornical organ, the subcommissural organ and the area postrema are situated at the confluence between ventricles while the neurohypophysis, the vascular organ of the lamina terminalis and the pineal gland line ventricular recesses.  

These observations raised the hypothesis that the suppression of ascending pathways from the DRN, possibly, 5-HTergic fibers, modifies the angiotensinergic or sodium sensing mechanisms of the subfornical organ involved in the control of the sodium appetite.  

The median preoptic nucleus (MnPO) receives afferent input from the subfornical organ, a circumventricular organ that has been shown to be necessary in mediating the full chronic hypertensive response to angiotensin II (ANG II) administration.  

These structures include the circumventricular organs (organum vasculosum of the lamina terminalis, subfornical organ, area postrema), some of the ependymal cells along the wall of the ventricles, tanycytes in the third ventricle's ependyma and the median eminence, as well as in the epithelial cells of the choroid plexus in the lateral, third and fourth ventricles.  

Compared to sham-depleted animals there was a significantly greater number of Fos-/FG-ir double-labeled cells in the subfornical organ, the organum vasculosum of the lamina terminalis and the median preoptic nucleus in rats that ingested NaCl.  

The brain targets for circulating Ang II are neurons in the area postrema (AP), subfornical organ (SFO), and possibly other circumventricular organs.  

There was a decreased level of nNOS mRNA and protein in the subfornical organ and the periventricular hypothalamic nucleus of the CIH rats, but no significant change in the supraoptic nucleus or the lateral hypothalamic area.  

The subfornical organ (SFO) is the center of the sensing responsible for the control of salt-intake behavior, where Na(x) channels are expressed in specific glial cells as the Na-level sensor.  

Ang II-like immunoreactivity was markedly increased in the subfornical organ (SFO).  

In a study appearing in this issue of the JCI, Sakai and associates use a combination of sophisticated transgenic techniques and stereotaxic microinjection of recombinant viral vectors to demonstrate a pivotal role in the regulation of thirst and salt appetite of angiotensin II generated in the subfornical organ in the brain (see the related article beginning on page 1088)..  

Fos-labeled neurons were quantified in the nucleus of the tractus solitarius (NTS), paraventricular nucleus (PVN), supraoptic nucleus (SON), and subfornical organ (SFO) after 1-h partial splenic vein occlusion (SVO) in conscious rats bearing balloon occluders around the splenic vein, telemetric pressure transducers in the gastric vein (splenic venous pressure), and abdominal aorta catheters (MAP).  

We have studied the effects of L-NG-nitro arginine methyl esther (L-NAME), L-arginine (LAR), inhibitor and a donating nitric oxide agent on the alterations of salivary flow, water intake, arterial blood pressure (MAP) and heart rate (HR) induced by the injection pilocarpine into the subfornical organ (SFO).  

In addition, glial cells isolated from the subfornical organ were sensitive to an increase in the extracellular sodium level, as analysed by an ion-imaging method.  

the sensory circumventricular organs (area postrema, vascular organ of laminae terminalis, subfornical organ), the astrocytes and a population of still undetermined cellular phenotype also showed marked STAT3 activation in response to PIPC.  

The vascular organ of the lamina terminalis and subfornical organ showed sustained but diminishing activation over the 14-day period.  

Bath applications of norepinephrine (NE; 20-50 microM) induced a prolonged and reversible suppression of inhibitory postsynaptic currents (IPSCs) and reduced paired-pulse depression evoked by stimulation in the subfornical organ and organum vasculosum lamina terminalis.  

Brains were subsequently processed for evaluation of Fos-like immunoreactivity (Fos-Li IR) in the organum vasculosum of the lamina terminalis (OVLT), the subfornical organ (SFO), and the median preoptic nucleus (MnPO).  

Fos-ir in the forebrain CVOs, the subfornical organ, and organum vasculosum laminae terminalis was consistently elevated only by hyperosmotic NaCl.  

Intracerebroventricular injections of orexin-A increase blood pressure and stimulate drinking, and the subfornical organ (SFO), a circumventricular structure implicated in autonomic control, is a potential site at which orexin may act to exert these effects.  

Direct and indirect evidence indicates that CIH leads to sympathoexcitation by two mechanisms: (1) augmentation of peripheral chemoreflex sensitivity (hypoxic acclimatization); and (2) direct effects on sites of central sympathetic regulation, such as the subfornical organ and the paraventricular nucleus of the hypothalamus.  

The subfornical organ (SFO) of the brain has long been considered a critical integrating center for the cardiovascular actions of the renin-angiotensin system (RAS).  

Less intense expression of CITED1 was also evident in medial preoptic area, subfornical organ, thalamus and cerebral cortex.  

The activation of the subfornical organ (SFO), a circumventricular organ, induces water intake and vasopressin release.  

In the subfornical organ, an area lacking the blood-brain barrier and sensitive to blood-borne angiotensin II, ACE2 was significantly increased in transgenic mice.  

Current-clamp recordings from cultured, subfornical organ neurons revealed significant effects of the peptide on membrane potential, suggesting this as a potential site of action.  

PKR2 mRNA is detected throughout the brain, with prominent expression in olfactory regions, cortex, thalamus and hypothalamus, septum and hippocampus, habenula, amygdala, nucleus tractus solitarius, and circumventricular organs such as subfornical organ, median eminence, and area postrema.  

Immunoreactive fibers were found in the telencephalic, diencephalic and mesencephalic areas such as the dorsal cortex, nucleus accumbens, lamina terminalis, preoptic area, mediodorsal region of the supraoptic nucleus, subfornical organ, nucleus of the paraventricular organ, subcommisural organ and periventricular grey region.  

Accumulating evidence suggests that structures within the lamina terminalis; the organum vasculosm of the lamina terminalis (OVLT), the median preoptic nucleus (MnPO) and/or the subfornical organ (SFO); are required for the development of DOCA-salt hypertension.  

The lamina terminalis consists of the organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus (MnPO) and subfornical organ. The prevalence of sleep-active neurons in the OVLT and subfornical organ is unknown.  

In order to study the participation of the subfornical organ (SFO) in this response we lesioned the nucleus and determined hormone secretion and c-fos expression in the paraventricular and supraoptic nuclei after administration of lipopolysaccharides (LPS) in rats.  

We hypothesized that both the pressor response and AVP secretion in response to ET-1 microinjection into subfornical organ (SFO) would be suppressed by ionotropic glutamatergic receptor antagonists in the paraventricular nucleus (PVN).  

Osmoreceptors within the organum vasculosum of the lamina terminalis and subfornical organ detect systemic hypertonicity. The subfornical organ mediates the dipsogenic actions of circulating angiotensin II and relaxin.  

Quantitative autoradiographic studies revealed that specific [ 3H]resveratrol binding sites are broadly distributed in the rat brain, with highest levels of labeling seen in the choroid plexus and subfornical organ.  

After 2 wk, there were significant decreases in AT(1) receptor mRNA and densities in the organum vasculosum of the lamina terminalis (OVLT), subfornical organ (SFO), and paraventricular nucleus (PVN).  

Isoproterenol significantly increased Fos IR in the hypothalamic paraventricular and supraoptic nuclei, the subfornical organ (SFO), and the organum vasculosum of the lamina terminalis, but had no effect on AT1 mRNA expression.  

Neurons in the subfornical organ (SFO), which has a role in fluid/electrolyte homeostasis, were potently activated by amylin.  

This disposgenic effect is likely mediated via amylin-sensitive neurones in the subfornical organ, a circumventricular structure, that like the area postrema does not present a blood-brain barrier.  

The CTa (shorter form) calcitonin receptor, dimerized with RAMP1 [ amylin 1 (a) receptor], appears to represent binding sites at the nucleus accumbens and the subfornical organ. Dense amylin binding is present at the circumventricular organs, including the subfornical organ, the organum vasculosum lateralis terminalis (OVLT), and the area postrema.  

In this study, we have examined the potential role of the subfornical organ (SFO), a circumventricular structure that lacks the normal blood-brain barrier, as a CNS site in which ghrelin acts to influence the hypothalamic centers controlling food intake.  

The present study was designed to examine whether glutamatergic receptor mechanisms modulate the release of acetylcholine (ACh) in the region of the subfornical organ (SFO) using intracerebral microdialysis methods in freely moving rats.  

The effects of noradrenaline (NA) and its analogs on subfornical organ (SFO) neurons in rat slice preparations were investigated by using whole cell patch-clamp recording.  

To clarify the regulation mechanism to the POMe, the innervation pattern of synapses made by axon terminals immunoreactive to beta-endorphin, neuropeptide Y and tyrosine hydroxylase onto POMe neurons projecting to the subfornical organ (SFO) was investigated in the rat.  

The ventricular ependyma (especially in the third one), the subfornical organ, the area postrema, the rat pineal body (in part), and the vascular organ of lamina terminalis were marked by intense immunopositivity.  

It stimulated increased MMP-2 expression in LGR7-expressing rat ventricular fibroblasts in a dose-dependent manner and, following infusion into the lateral ventricle of the brain, stimulated water drinking in rats, activating LGR7 receptors located in the subfornical organ.  

When Na(x) cDNA was introduced into the brain of the knockout mice with an adenoviral expression vector, only animals that received a transduction of the Na(x) gene into the subfornical organ (SFO) among the CVOs recovered salt-avoiding behavior under dehydrated conditions.  

In animal studies, beta-galactosidase staining and Ang receptor binding assays showed expression of shRNA and downregulation of Ang AT1 receptors in the subfornical organ and NTS/DVN by >70%.  

In response to Ang II, apocynin-sensitive production of superoxide increased significantly in the nuclei of the anterior hypothalamus, in the subfornical organ, and in the paraventricular nucleus of the hypothalamus.  

Projections of the ventral nucleus are a subset of those generated by the magnocellular nucleus, with the obvious difference that the ventral nucleus does not project detectably to Barrington's nucleus, the subfornical organ, the median preoptic and parastrial nuclei, the neuroendocrine system, and midbrain orofacial motor-related regions..  

They fall into eight general categories: humeral sensory-related (subfornical organ and median preoptic nucleus, involved in initiating drinking behavior and salt appetite), neuroendocrine system (magnocellular: oxytocin, vasopressin; parvicellular: gonadotropin-releasing hormone, somatostatin, thyrotropin-releasing hormone, corticotropin-releasing hormone), central autonomic control network (central amygdalar nucleus, BST anterolateral group, descending paraventricular hypothalamic nucleus, retrochiasmatic area, ventrolateral periaqueductal gray, Barrington's nucleus), hypothalamic visceromotor pattern-generator network (five of six known components), behavior control column (ingestive: descending paraventricular nucleus; reproductive: lateral medial preoptic nucleus; defensive: anterior hypothalamic nucleus; foraging: ventral tegmental area, along with interconnected nucleus accumbens and substantia innominata), orofacial motor control (retrorubral area), thalamocortical feedback loops (paraventricular, central medial, intermediodorsal, and medial mediodorsal nuclei; nucleus reuniens), and behavioral state control (subparaventricular zone, ventrolateral preoptic nucleus, tuberomammillary nucleus, supramammillary nucleus, lateral habenula, and raphé nuclei).  

These areas included the subfornical organ, median preoptic nucleus, organum vasculosum of the lamina terminalis, and paraventricular nuclei in the forebrain, and the tractus solitarius nuclei, lateral parabrachial nuclei in the hindbrain.  

Since Ang II also plays a role in controlling reproductive functions, such as luteinizing hormone and prolactin secretion, the objective of the present study was to evaluate the regulation of Ang II receptors by estradiol (E(2)) and progesterone (P) in areas of the brain involved in homeostatic and reproductive functions, such as the locus coeruleus (LC), median preoptic nucleus (MnPO) and subfornical organ (SFO).  

In this context, excitability of MnPO neurones is controlled by fast GABAergic, glutamatergic and angiotensinergic projection from the subfornical organ (SFO).  

In addition, glial cells isolated from the subfornical organ, one of the CVOs, were sensitive to an increase in the extracellular sodium level, as analyzed by an ion-imaging method.  

METHODS: We performed an extensive immunohistological study on the area postrema (AP), the subfornical organ (SFO), the organum vasculosum of the lamina terminalis (OVLT) and the median eminence (ME) in frozen brain sections from healthy SJL mice and mice suffering from EAE.  

The two isoforms showed similar distributions in the subfornical organ and in tanycytes of the third ventricle.  

Additional immunostained cells were found in the septum, bed nucleus of the stria terminalis, subfornical organ and subcommissural organ.  

Although angiotensin II inhibits transient outward K+ currents (I(A)s) in subfornical organ neurones, there is no evidence concerning which Kv channels are involved. We investigated I(A)-generating Kv channels in dissociated rat subfornical organ neurones, using molecular, electrophysiological and pharmacological techniques, and studied the effects of angiotensin II. These results suggest that the fast recovery component of the tetraethylammonium-resistant I(A) in subfornical organ neurones depends upon Kv4, and that it can be modulated by angiotensin II..  

There was no significant change in GAPDH, beta-actin, 36B4 mRNA and 28S rRNA at the subfornical organ and the hippocampus..  

A discrete number of c-Fos protein immunoreactive nuclei could be observed in some circumventricular organs, including the vascular organ of terminal lamina (OVLT) and subfornical organ (SFO) and in the nucleus of solitary tract near the area postrema, but only in specimens from sensitized rats.  

The effects of resveratrol on the discharges of neurons in rat subfornical organ (SFO) slices were examined by using extracellular recording technique.  

Under water ad libitum conditions, there were no differences in AT1b mRNA expression in medial periventricular, anterior third ventricle (AV3V), and subfornical organ (SFO) between controls and AT1aKO.  

High densities of LGR7 mRNA hybridization were detected in deep layers of neocortex, hypothalamic paraventricular and supraoptic nuclei and within hippocampal subiculum and CA3, the basolateral amygdala and subfornical organ.  

Low to moderate densities were detected in olfactory bulb (periglomerular layer), cingulate cortex, subfornical organ, hippocampal CA2/dentate hilus, amygdala, hypothalamus, and thalamus.  

In contrast, significant increases in the BBB leakage of sodium fluorescein, a much smaller molecule, were observed 1 and 2 days after the induction of colitis, in and around the circumventricular organs; the organum vasculosum of the lamina terminalis, subfornical organ and median eminence of the hypothalamus.  

Similar to ANG II, ANG III induced the expression of c-Fos, c-Jun, and Krox-24 in four brain regions, subfornical organ, median preoptic area, paraventricular nucleus, and supraoptic nucleus of the hypothalamus, with the same efficacy.  

The result demonstrated that the vasopressinergic neurons in PVN could be excited by peripheral hypertonic stimulation, and this excitation might be mediated by angiotensin II fibers projecting from subfornical organ to PVN..  

Of these, the subfornical organ (SFO) has been shown to be involved in many of the acute dipsogenic and pressor effects of AngII, but much less is known about the role of the SFO in the chronic effects of AngII.  

The subfornical organ (SFO), one of the brain circumventricular organs, is known to mediate some of the central effects of angiotensin II related to sodium and water homeostasis.  

Furthermore, our data suggest that both the postolfactory eminence and the bed nucleus of the pallial commissure are not part of the septal complex, rather, the postolfactory eminence seems to be comparable to the mammalian primary olfactory cortex, whereas the bed nucleus may be analogous to the mammalian subfornical organ..  

In the rat, Y1-R mRNA expression was also seen in the subfornical organ, anterior hypothalamic area, dorsal hypothalamic area, and in the lateral hypothalamic area.  

These results suggest that ibotenic lesion of DRN promote an increase of the brain angiotensinergic response, possibly settled within the subfornical organ, through paradigms which increase circulating ANG II levels.  

In addition, the fetal organum vasculosum of the lamina terminalis and the subfornical organ were activated.  

We studied the effects of spontaneous high blood pressure and the captopril treatment on the subfornical organ (SFO) of rats.  

The lamina terminalis was severed by a horizontal knife cut through the anterior commissure to determine the effects of a disconnection of the subfornical organ (SFO) on drinking and Fos-like immunoreactivity (Fos-ir) in the rat brain in response to an intragastric load of hypertonic saline (5 ml/kg of 1.5 M NaCl by gavage).  

In this study, we compared angiotensin (Ang) receptor density in the subfornical organ (SFO) and paraventricular nucleus (PVN) of a) brain angiotensinogen deficient rats (ASrAogen); b) those with high levels of brain Ang II [ (mRen2)27]; c) Hannover Sprague Dawley (SD) rats at 48 and 68 wks of age.  

We now show in Crl:CD1(ICR) mice that peripheral injection of the ANG II type 1 receptor antagonist losartan was sufficient to prevent this induction of Fos-ir in the subfornical organ (SFO).  

The immunoreactive cells of HO-1 were mainly located at the choroid plexuses and subfornical organ (SFO), as well as in regions around the "sleeve-like" lesion foci, all of which were coincident with the locations of lesions of EAE.  

Here we show that the subfornical organ (SFO) is the principal site for the control of salt-intake behavior, where the Na(x) channel is the Na-level sensor.  

We investigated the effect of endothelins (ETs) on receptor-mediated phosphoinositides (PI) turnover in whole subfornical organ (SFO) and median eminence (ME).  

Previous studies clearly demonstrated acute actions of angiotensin II (ANG II) at one of the central circumventricular organs, the subfornical organ (SFO), but studies demonstrating a role for the SFO in the chronic actions of ANG II remain uncertain.  

The regions examined were the organum vasculosum laminae terminalis (OVLT), the median preoptic nucleus (MnPO), the subfornical organ (SFO), the paraventricular nucleus (PVN), the supraoptic nucleus of the hypothalamus, the nucleus of the solitary tract (NTS), and the area postrema (AP).  

Recently, a similar cardiovascular alteration has been reported after the electrolytic lesion of the anteroventral region of the third ventricle affecting the connections of the subfornical organ (SFO).  

The aim of this study was to investigate the effects of agmatine (Agm) on the electrical activity of neurons in subfornical organ (SFO) slices using extracellular recording technique.  

In many previous studies, one or the other forebrain circumventricular organ, the subfornical organ (SFO) or organum vasculosum laminae terminalis (OVLT), was lesioned to test whether it was critical for the behavioral or physiological responses to sodium depletion and hypernatremia.  

NaCl injection resulted in rapid activation of the subfornical organ (SFO), organum vasculosum lamina terminalis (OVLT), and periventricular regions and the lateral hypothalamic area (LHA), then of the paraventricular hypothalamic nucleus (PVN) and supraoptic nucleus (SON).  

We also tested the hypothesis that the subfornical organ (SFO) is a site responsible for the alterations in body temperature and aerial righting reflex mediated by ethanol and for the modulation of ethanol consumption in rats.  

AT(1) receptors in the subfornical organ, the hypothalamic paraventricular nucleus (PVN), and the median eminence are involved in the regulation of the stress response.  

Our studies of osmoregulatory drinking in the sheep and rat have produced evidence that osmoreceptors for thirst exist in the dorsal cap of the organum vasculosum of the lamina terminalis (OVLT) and in the periphery of the subfornical organ, and possibly also in the median preoptic nucleus. In the rat, the hormones angiotensin II and relaxin act on neurons in the periphery of the subfornical organ to stimulate drinking.  

Other defects displayed by homozygous mutants were ependymal denudation, subventricular cavitations and edema, and underdevelopment of the pineal gland and subfornical organ.  

The highest levels are present within the subfornical organ (SFO) and the olfactory bulbs.  

Infusion of Ang II (600 ng x kg(-1) x min(-1)) over a 2-week period in mice caused a gradually developing hypertension that was correlated with marked elevations in O2*- production specifically in the subfornical organ (SFO), a brain region lying outside the blood-brain barrier and known to be a primary sensor for blood-borne Ang II.  

Intracolonic TNBS induced c-fos mRNA expression in brain nuclei involved in the autonomic, behavioral, and neuroendocrine response to a stimulus (PVN, amygdala, locus coeruleus, parabrachial nucleus, nucleus of the solitary tract) and in circumventricular organs (lamina terminalis, subfornical organ, area postrema).  

Our previous studies show that: (1) AV3V stimulation by glutamate produces a fall in blood pressure; (2) there is an AngII pressor system composed of the lateral hypothalamus/perifornical region (LH/PF), subfornical organ (SFO), nucleus paraventricularis (NPV) and rostral ventrolateral medulla (RVL).  

The subfornical organ (SFO), median preoptic nucleus (MnPO), and organum vasculosum lamina terminalis (OVLT), which are associated with the lamina terminalis, are important in the control of body fluid balance.  

The lamina terminalis, located in the anterior wall of the third ventricle, is comprised of the subfornical organ, median preoptic nucleus (MnPO) and organum vasculosum of the lamina terminalis (OVLT). The subfornical organ and OVLT are two of the brain's circumventricular organs that lack the blood-brain barrier, and are therefore exposed to the ionic and hormonal environment of the systemic circulation. There is considerable evidence that physiological osmoreceptors subserving vasopressin release are located in the dorsal cap region of the OVLT and possibly also around the periphery of the subfornical organ and in the MnPO. The circulating peptide hormones angiotensin II and relaxin also have access to peptide specific receptors (AT(1) and LGR7 receptors, respectively) in the subfornical organ and OVLT, and both angiotensin II and relaxin act on the subfornical organ to stimulate water drinking in the rat. Studies that combined neuroanatomical tracing and detection of c-fos expression in response to angiotensin II or relaxin suggest that both of these circulating peptides act on neurones within the dorsal cap of the OVLT and the periphery of the subfornical organ to stimulate vasopressin release..  

Autoradiographic receptor binding studies demonstrated an increase in brain AT(1) expression in the subfornical organ and the vascular organ of the lamina terminalis in the 9% offspring.  

Single stereotaxic microinjections of Ad-Cre or FIV-Cre into specific nuclei along the subfornical organ-hypothalamic-hypophysial and brain stem-parabrachial axes resulted in robust and highly localized gene deletion as early as 7 days and for as long as 3 wk in a reporter mouse model in which Cre recombinase activates beta-galactosidase expression.  

The G-protein-coupled receptor prokineticin receptor 2 (PKR-2), which binds Bv8 and PK-2 with high affinity, is mainly expressed in the piriform cortex, paraventricular thalamic nucleus, parataenial nucleus (PT), SCN, hypothalamic paraventricular (PVH) and dorsomedial (DMH) nuclei, arcuate nucleus (ARC) and subfornical organ (SFO) of the rat brain.  

GnRH-IR cells and fibres were also found in the subfornical organ.  

Using these reporter transgenes as sensitive markers for renin and angiotensinogen expression, we conclude that both proteins are coexpressed in the parabrachial nucleus and central nucleus of the amygdala and are in adjacent cells in the RVLM, reticular formation, bed nucleus of the stria terminalis, subfornical organ, and CA1-3 region.  

In the present work, we show that the OCT3 transporter is found throughout the brain and highly expressed in regions regulating fluid exchange, including circumventricular organs such as area postrema and subfornical organ (SFO), and in other structures implicated in the sensing of changes in blood osmolarity and regulation of salt and water ingestion.  

IL-1R1-immunoreactive vessels were seen throughout the brain, but concentrated in the preoptic area, subfornical organ, supraoptic hypothalamus, and to a lesser extent in the paraventricular hypothalamus, cortex, nucleus of the solitary tract, and ventrolateral medulla.  

Experiments were performed in the male Wistar rat to investigate the projections from cardiovascular responsive sites in the ventrolateral medulla (VLM) to the subfornical organ (SFO).  

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.  


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