Subcommissural organ-Reissner's fiber complex plasticity in two animal models of copper intoxication and modulatory effect of curcumin: Involvement of serotonin.

Metal neurotoxicity is a universal health preoccupation. Previous data revealed an obvious neurochemical impairment induced by metal elements as copper. This investigation was conducted to study the subcommissural organ (SCO) response to acute and subchronic Cu exposure as well as its serotoninergic innervation in Wistar rats, and the probable protective potential of curcumin in these toxicological circumstances. By mean of immunohistochemistry using antibodies against Reissner's fiber (RF) and serotonin (5-HT) in acute model (10 mg/kg i.p. for 3 days) and subchronic model (0.125% in drinking water for six weeks), we noted a significant decrease of RF-immunoreactivity and a whole amplified 5-HT innervation of SCO and ventricular borders in intoxicated rats. Co-treatment with curcumin-I (30 mg/kg B.W) has shown a beneficial effect, reinstating both SCO secretory activity and serotoninergic innervation damaged by Cu exposure. This data revealed for the first time an obvious response of SCO-RF complex to Cu intoxication as well as the neuroprotective effect of curcumin-I. Thus, SCO could play a fundamental role in the strategies of brain resistance to neurotoxicity induced by metal elements in rats, and may be used as biomarker to assist in the diagnosis of this neurotoxicological conditions in rodents.

Evidence of a subcommissural organ involvement in the brain response to lead exposure and a modulatory potential of curcumin.

Substantial evidence supports the neurochemical vulnerability to lead (Pb) as one of the most potent neurotoxic heavy metals. In the present study, we aimed to assess: (i) The subcommissural organ (SCO) responsiveness as a secretory circumventricular organ to chronic and acute Pb intoxication together with its serotoninergic innervation. (ii) The possible restorative effect of curcumin against Pb intoxication under the same pathological conditions. We used immunohistochemistry with antibodies against Reissner's fiber and serotonin [5-hydroxytryptophan (5-HT)] in Wistar rats following chronic as well as acute Pb administration, respectively, at 25 mg/kg intraperitoneally for 3 days and 0.3% in drinking water from the intrauterine stage until 2 months of adult age. Our data showed a significant decrease in Reissner's fiber material immunoreactivity concomitant with an overall increased 5-HT innervation of the SCO and the ventricular borders. Coadministration of curcumin (50 mg/kg body weight) restores this impairment by reversing the effect of chronic and acute Pb on the secretory activity and the 5-HTergic innervation of the SCO. The investigation showed, on the one hand, the involvement of the SCO in the response to heavy metals, especially Pb, and on the other, the beneficial corrector role of curcumin. As a part of the circumventricular organ, known as a privileged area of brain-blood exchanges, the SCO may play a key role in the mechanism of brain defense against heavy metal neurotoxicity in rats.

Chronic aluminum intoxication in rat induced both serotonin changes in the dorsal raphe nucleus and alteration of glycoprotein secretion in the subcommissural organ: Immunohistochemical study.

Aluminum (Al) causes multiple impairments in several body systems including the central nervous system. In fact, Al exposure has been mostly associated with neurological dysfunctions that occur in some brain diseases. The effect of Al neurotoxicity on the dopaminergic system is well documented, but this effect on the serotoninergic system is poorly studied. The aim of this work is to evaluate the effect of chronic Al intoxication (0.3% of aluminum chloride exposure from the intra-uterine age until 4 months of adult age) on dorsal raphe nucleus (DRN) which is the main source of serotonin, and also on the glycoprotein secretion of subcomissural organ (SCO), receiving important serotoninergic innervation. This will be executed using immunohistochemistry procedure, with both the anti serotonin and the anti Reissner's fiber antibodies in the rat. Our results showed a significant increase of serotonin immunoreactivity in the DRN, accompanied by a noticeable decrease of RF immunoreactivity in the SCO ependymocytes. This study provides further evidence confirming the toxic effect of Al exposure on serotonin neurotransmission in the brain likely through increased synthesis or decreased release. Al exposure was also shown to decrease RF glycoprotein which is involved in the detoxification of cerebrospinal fluid.

A sensitive method to analyse the effect of putative regulatory ligands on the release of glycoprotein from primary cultures of dispersed bovine subcommissural organ cells.

The subcommissural organ (SCO) releases into the cerebrospinal fluid (CSF) large glycoproteins that polymerize forming the Reissner's fibre (RF), which is involved in CSF circulation and homeostasis. We obtained high purity primary cultures of bovine secretory SCO cells and measured glycoprotein release by a reliable and sensitive ELISA method. We also analysed the effect of regulatory ligands known to control the secretory activity of the SCO. Cells cultured for short time (4h) released a high amount of glycoproteins that decreased with time. In young cultures, ATP increased and serotonin inhibited secretion rate. By contrast the acetylcholine agonist carbachol and high potassium did not evoke any detectable change in SCO glycoprotein release. These results support not only the suitability of the methodological approach but an important role of both ATP and serotonin in regulating SCO secretory activity as well.

Physiological response of bovine subcommissural organ to endothelin 1 and bradykinin.

The circumventricular organs (CVOs) regulate certain vegetative functions. Receptors for bradykinin (BDK) and endothelin (ET) have been found in some CVOs. The subcommissural organ (SCO) is a CVO expressing BDK-B2 receptors and secreting Reissner's fiber (RF) glycoproteins into the cerebrospinal fluid. This investigation was designed to search for ET receptors in the bovine SCO and, if found, to study the functional properties of this ET receptor and the BDK-B2 receptor. Cryostat sections exposed to (125)I ET1 showed dense labeling of secretory SCO cells, whereas the adjacent ciliated ependyma was devoid of radiolabel. The binding of (125)I ET1 was abolished by antagonists of ETA and ETB receptors. The intracellular calcium concentration ([Ca(2+)](i)) was measured in individual SCO cells prior to and after exposure to ET1, BDK, or RF glycoproteins. ET1 (100 nM) or BDK (100 nM) caused an increase in [Ca(2+)](i) in 48% or 53% of the analyzed SCO-cells, respectively. RF glycoproteins had no effect on [Ca(2+)](i) in SCO cells. ET and BDK evoked two types of calcium responses: prolonged and short responses. Prolonged responses included those with a constant slow decline of [Ca(2+)](i), biphasic responses, and responses with a plateau phase at the peak level of [Ca(2+)](i). ET1-treated SCO explants contained a reduced amount of intracytoplasmic AFRU (antiserum to RF glycoproteins)-immunoreactive material compared with sham-treated control explants. Our data suggest that ET1 and BDK regulate [Ca(2+)](i) in bovine SCO cells, and that the changes in [Ca(2+)](i) influence the secretory activity of these cells.

Immunohistochemical evaluation of the effect of lead exposure on subcommissural organ innervation and secretion in Shaw's Jird (Meriones shawi).

The secretory activity of subcommissural organ cells is controlled by various extrinsic and intrinsic factors. Lead has been recognised as a neurotoxic heavy metal, since it induces morphological and functional abnormalities in the brain. In this work, we examined the effect of lead exposure on the subcommissural organ (SCO), a brain gland known by its secretion of Reissner's fiber (RF) in cerebro-spinal fluid. Glycoprotein secretion and serotonin (5HT) innervation of the SCO was examined after acute and chronic lead exposures in the sub-desert rodent Meriones shawi. Lead exposures were achieved by, respectively, intra-peritoneal injection of 25 mg/kg body weight of lead acetate for 3 days and 0.5% of lead acetate in the drinking water over 4 months until adult age. 5HT and RF immunolabeling in the SCO revealed several serotoninergic fibers reaching the SCO and abundant secretory material. An increase in both 5HT innervation and secretory material of the SCO was recorded after both acute and chronic lead exposure. These results show that lead exposure affects the serotonergic innervation of the SCO. Moreover, the enhancement of SCO secretion suggests a role of this gland in neuroprotection and lead detoxification of the brain in Meriones shawi.

Bovine subcommissural organ displays spontaneous and synchronous intracellular calcium oscillations.

The subcommissural organ (SCO) is an ependymal brain gland that secretes into the cerebrospinal fluid glycoproteins that polymerize, forming Reissner's fiber (RF). The SCO-RF complex seems to be involved in vertebrate nervous system development, although its role in adults is unknown. Furthermore, its physiology is still greatly undetermined, and little is known about the release control of SCO secretion and the underlying intracellular mechanisms. In this report, we show that up to 90% of 3-5-day-old in vitro SCO cells from both intact and partially-dispersed SCO explants displayed spontaneous cytosolic Ca2+ oscillations. The putative role of these spontaneous calcium oscillations in SCO secretory activity is discussed taking into consideration several previous findings. Two distinct subpopulations of SCO cells were detected, each one containing cells with synchronized calcium oscillations. A possible existence of different functional domains in SCO is therefore discussed. Oscillations persisted in the absence of extracellular Ca2+, indicating the major involvement of Ca2+ released from internal stores. Depolarization failed to induce intracellular calcium increases, although it disturbed the oscillation frequency, suggesting a putative modulator role of depolarizing agonists on the calcium oscillating pattern through voltage-gated calcium channels. Carbachol, a cholinergic agonist, evoked a switch in Ca2+ signaling from a calcium oscillating mode to a sustained and increased intracellular Ca2+ mode in 30% of measured cells, suggesting the involvement of acetylcholine in SCO activity, via a calcium-mediated response.

Transcription factor CREB and its stimulus-dependent phosphorylation in cell and explant cultures of the bovine subcommissural organ.

The subcommissural organ (SCO) is an ependymal brain gland that synthesizes and secretes glycoproteins. Very little is known about the signal transduction cascades operating in this organ and their impact on gene expression. An important transcription factor that regulates gene expression in glial cells and neurons is the cyclic-AMP-responsive element binding protein (CREB), which is activated by phosphorylation of the serine residue 133. Here, we analyzed the presence of CREB in bovine SCO cells and its phosphorylation by drugs that activate cyclic-AMP-dependent or calcium-dependent signal transduction pathways. We also investigated the effects of three natural signaling molecules, serotonin (5HT), substance P (SP) and ATP, on CREB phosphorylation and on the second messengers cyclic AMP and calcium. Investigations were performed with cell and explant cultures by using immunocytochemistry, immunoblot, enzyme-linked immunosorbent assay, and the Fura-2 technique. A strong immunosignal for total (phosphorylated and unphosphorylated) CREB was found in virtually all SCO cells. Total CREB levels did not change upon stimulation. Phosphorylated (p)CREB levels were low in unstimulated cells and significantly elevated by drugs that increase the levels of cyclic AMP or free calcium ions. pCREB was also induced by SP and ATP; both substances increased the intracellular calcium concentration but did not affect the formation of intracellular cyclic AMP. 5HT did not influence the phosphorylation of CREB, the intracellular calcium concentration, or the formation of cyclic AMP. Our data identify CREB as an SCO transcription factor that can be activated by the second messengers cAMP and calcium. SP and ATP stimulate the phosphorylation of CREB apparently via a calcium-dependent mechanism and are thus involved in the control of gene expression in the bovine SCO.

Effects of neuroactive substances on the activity of subcommissural organ cells in dispersed cell and explant cultures.

The subcommissural organ (SCO), an ependymal (glial) circumventricular organ, releases glycoproteins into the cerebrospinal fluid; however, the regulation of its secretory activity is largely unknown. To identify neuroactive substances that may regulate SCO activity, we investigated immunocytochemically identified bovine SCO cells by means of calcium imaging. This analysis was focused on: (1) serotonin (5HT) and substance P (SP), immunocytochemically shown to be present in axons innervating the bovine SCO; and (2) ATP, known to activate glial cells. 5HT had no effect on the intracellular calcium concentration ([Ca(2+)](i)), and its precise role remains to be clarified. SP elicited rises in [Ca(2+)](i) in approx. 30% and ATP in even 85% of the analyzed SCO cells. These effects were dose-dependent, involved NK(3) and P2Y(2) receptors linked to G protein and phospholipase C (PLC) activation, and could not be mimicked by forskolin or 8-bromo-cAMP. In 50% of the SP-sensitive cells, the increases in [Ca(2+)](i) comprised calcium release from thapsigargin-sensitive intracellular stores and an influx of extracellular calcium via protein kinase C (PKC)-induced opening of L-type voltage-gated calcium channels (VGCCs). In the remaining SP-sensitive cells, the increase in [Ca(2+)](i) was caused exclusively by influx of extracellular calcium via VGCCs of the L-type. In all ATP-sensitive cells the increase in [Ca(2+)](i) involved calcium release from thapsigargin-sensitive intracellular stores and a PKC-mediated influx of extracellular calcium via L-type VGCCs. Our data suggest that SP and ATP are involved in regulation of the activity of SCO cells.

The dispersed cell culture as model for functional studies of the subcommissural organ: preparation and characterization of the culture system.

The subcommissural organ (SCO) is an enigmatic secretory gland of the brain, which is believed to be derived from ependymal (glial) precursor cells. We here developed a dispersed cell culture system of the bovine SCO as an approach to functional analyses of this brain gland. Tissue of the bovine SCO obtained from the slaughterhouse was papain dissociated either directly after dissection or after preparation of SCO explants. The latter had been maintained for 4-6 weeks in organ culture. The dispersed cells were cultured for up to 14 days and continuously tested for their secretory state by immunostaining of their secretory product. With respect to the morphology of the SCO cells (shape, processes, nucleus), no difference was found between the culture of freshly dissociated SCOs and that of dissociated SCO explants. In all cases, the dissociation caused a dedifferentiation; typical elongated cells were formed increasingly after 1 day of culture. Thereafter, only the cellular size increased, whereas the shape and the viability of the cells remained unchanged. Proliferating SCO cells were never observed. The culture obtained from fresh SCO tissue contained more glia cells and fibrocytes than the culture prepared from SCO explants. The proliferation of glia cells and fibrocytes was suppressed by blocking the mitotic activity with cytosine-beta-D-arabino furanoside (CAF). The cytophysiological features of the cultured dispersed cells of both origins did not differ as demonstrated by classical histology, by immunocytochemistry for the secretory products of the SCO, by the characteristics of calcium influx into the cytoplasm ([Ca2+]i) and cyclic adenosine monophosphate (cAMP) after stimulation with adenosine-5-triphosphate, substance P or serotonin, and by the activation of the transcription factor cAMP-responsive element-binding protein. Because of the maintenance of their viability, their capacity to release the secretory product into the culture medium, their receptive capacity, and their signal transduction pathways, we conclude that the dispersed cell culture system, especially that obtained from SCO explants, represents an appropriate and useful model for functional studies of the mammalian SCO.

Secretory activity and serotonin innervation of lizard's subcommissural organ.

We investigated immunohistochemically the subcommissural organ (SCO) glycoprotein secretion, its serotoninergic (5-HT) innervation and the possible control of this innervation upon the SCO activity in lizards (Agama impalearis, Saurodactylus mauritanicus and Eumeces algeriensis). Inside the SCO, interspecific differences in the intensity and the distribution of both secretory product and 5-HT nerve fibers were observed. Compared with Agama and Eumeces, the SCO of Saurodactylus displayed intense secretory products and several 5-HT fibers. In Saurodactylus, i.p. injection of parachlorophenylalanine, a potent inhibitor of 5-HT synthesis, produced a marked decrease of SCO secretory product. We report in this study species differences of the lizard SCO secretory activity and its possible physiological control by 5-HT innervation, as previously demonstrated in mammals.

Secretory activity and serotonin innervation of subcommissural organ.

We investigated immunohistochemically the subcommissural organ (SCO) glycoprotein secretion, its serotoninergic (5-HT) innervation and the possible control of this innervation upon the SCO activity in lizards (Agama impalearis, Saurodactylus mauritanicus and Eumeces algeriensis). Inside the SCO, interspecific differences in the intensity and the distribution of both secretary product and 5-HT nerve fibers were observed. Compared with Agama and Eumeces, the SCO of Saurodactylus displayed intense secretory products and several 5-HT fibers. In Saurodactylus, i.p. injection of parachlorophenylalanine, a potent inhibitor of 5-HT synthesis, produced a marked decrease of SCO secretory product. We report in this study species differences of the lizard SCO secretory activity and its possible physiological control by 5-HT innervation, as previously demonstrated in mammals.

Circumventricular organs: definition and role in the regulation of endocrine and autonomic function.

1. The circumventricular organs (CVO) are structures that permit polypeptide hypothalamic hormones to leave the brain without disrupting the blood-brain barrier (BBB) and permit substances that do not cross the BBB to trigger changes in brain function. 2. In mammals, CVO include only the median eminence and adjacent neurohypophysis, organum vasculosum lamina terminalis, subfornical organ and the area postrema. 3. The CVO are characterized by their small size, high permeability and fenestrated capillaries. The subcommissural organ is not highly permeable and does not have fenestrated capillaries, but new evidence indicates that it may be involved in the hypertension produced by aldosterone acting on the brain. 4. Feedback control of corticotropin-releasing hormone (CRH) secretion is exerted by free steroids diffusing into the brain, but substances such as cytokines and angiotensin II act on CVO to produce increases in CRH secretion. Gonadal steroids also diffuse into the brain to regulate gonadotrophin-releasing hormone secretion. Thyrotropin-releasing hormone secretion is regulated by thyroid hormones transported across cerebral capillaries. However, CVO may be involved in the negative feedback control of growth hormone and prolactin secretion.

Subcommissural organ-Reissner's fiber complex of the teleost Clarias batrachus responds to GABA treatment.

Subcommissural organ (SCO) is a highly specialized ependymal gland located in the roof of the third ventricle. The secretory products of the SCO, which condense to form Reissner's fiber (RF), were recently found to cross-react with the anti-calcitonin antibody. To understand the mechanisms regulating the formation of the RF and the possible function of these discrete structures, we studied the response of the SCO-RF complex to intracranially administered GABA, using immunocytochemical labeling with anti-calcitonin antibody. Although the SCO-RF complex of control fish was intensely immunostained, 1 h after GABA treatment, the ependymal cells revealed partial loss of immunoreactivity; the RF showed occasional loss of immunoreactivity with its diameter increased by about 56% of the control value. Following 2 h of GABA treatment, the SCO revealed dramatic loss of calcitonin-like immunoreactivity from the ependymal cells. The RF showed a dual response in this group, while in some segments the RF appeared conspicuously thick, elsewhere it appeared thin. The mean diameter was, however, not significantly different from the normal. Following 4 h of GABA treatment, while calcitonin-like immunoreactive material made its reappearance in the SCO, the RF diameter was uniformly reduced to about 35% of the control value. The responses by the RF as well as the SCO to intracranially administered GABA were blocked by pretreatment with bicuculline, a GABA(A) receptor antagonist. The results suggest that GABA, acting via GABA(A) receptors, may trigger the release of secretory material from the SCO and induce histomorphological changes in the RF indicative of discharge of stored material.

Neuraminidase injected into the cerebrospinal fluid impairs the assembly of the glycoproteins secreted by the subcommissural organ preventing the formation of Reissner's fiber.

Neuraminidase was injected into the cerebrospinal fluid of normal rats to investigate the assembly and fate of the desialylated Reissner's fiber glycoproteins. It was established that a single injection of neuraminidase cleaved the sialic acid residues of the Reissner's fiber glycoproteins that had been assembled before the injection, and of the molecules that were released over a period of at least 4 h after the injection. These desialylated glycoproteins underwent an abnormal assembly that led to the formation of spheres instead of a fiber. The number of these spheres increased during the 4-h period following the injection, indicating that neuraminidase did not prevent the secretion of the Reissner's fiber glycoproteins into the cerebrospinal fluid. The spheres remained attached to the surface of the subcommissural organ and became intermingled with infiltrating cells, many of which were immunocytochemically identified as macrophages. The latter were seen to contain immunoreactive Reissner's fiber material. It is concluded that the desialylated Reissner's fiber glycoproteins forming the spheres underwent an in situ degradation by macrophages, thus resembling the normal process undergone by the Reissner's fiber glycoproteins reaching the massa caudalis.

Secretory glycoproteins of the rat subcommissural organ are N-linked complex-type glycoproteins. Demonstration by combined use of lectins and specific glycosidases, and by the administration of Tunicamycin.

Two experimental protocols were used to investigate the secretory glycoproteins of the subcommissural organ (SCO). Protocol I: Lectins, specific exoglycosidases and immunocytochemistry were sequentially applied to the same section or to adjacent semithin sections of the rat SCO fixed in Bouin's fluid and embedded in methacrylate. Lectins used: concanavalin A (con A), wheat germ agglutinin, Limulus polyphemus agglutinin, Ricinus communis agglutinin and Arachis hypogeae agglutinin. Glycosidases used: neuroaminidase, beta-galactosidase, alpha-mannosidase, alpha-glucosidase and beta-N-acetyl-glucosaminidase. For immunocytochemistry an antiserum against bovine Reissner's fiber (AFRU) was used. Lectins and glycosidases were used in sequences that allowed the cleaved sugar residue to be identified as well as that appearing exposed as a terminal residue. This approach led to the following conclusions: (1) the terminal sugar chain of the secreted glycoproteins has the sequence sialic acid-galactose-glucosamine-; (2) the con A-binding material present in the rough endoplasmic reticulum corresponds to mannose; (3) the apical secretory granules and Reissner's fibers displayed a strong con A affinity after removing sialic acid, thus indicating the presence of internal mannosyl residues in the secreted material; (4) after removing most of the sugar moieties the secretory material continued to be strongly immunoreactive with AFRU. Protocol II: Rats were injected into the lateral ventricle with Tunica-mycin and killed 12, 24, 50 and 60 h after the injection. The SCO of rats from the last two groups showed a complete absence of con A binding sites. The results from the two experiments confirm that the secretory glycoproteins of the rat SCO are N-linked complex-type glycoproteins with the conformation previously suggested (Rodríguez et al. 1986).

Neuronal control of [3H]GABA uptake in the ependymocytes of the subcommissural organ: an in vivo model of neuron-glia interaction.

The rat subcommissural organ (SCO) is a particular but adequate paradigm for the approach, in vivo, to some aspects of neuron-glia interaction in gamma-aminobutyric acid (GABA) uptake. The rat SCO ependymocytes (the main component of this structure lying at the junction of the aqueduct and the third ventricle) accumulate [3H]GABA by a highly specific uptake mechanism and receive a serotoninergic input forming typical synaptic contacts. It seems that there is a correlation between the capacity of the rat SCO ependymocytes to take up [3H]GABA and the presence of a serotonin (5-HT) innervation. Indeed, in the newborn rat, no uptake of [3H]GABA was observed before the onset of this innervation and the increased [3H]GABA accumulation in the SCO was correlated with the appearance of the 5-HT terminals in the SCO. Moreover, in the mouse, whose SCO is devoid of a 5-HT innervation, no accumulation of [3H]GABA was observed in the SCO ependymocytes. Thus, the 5-HT innervation could be involved directly or indirectly in the onset of the GABA uptake carriers. On the other hand, in adult rats parachlorophenylalanine (pCPA) treatment decreased the 5-HT content of the SCO, and increased [3H]GABA accumulation; such an augmentation was not observed when rats were treated with pCPA plus 5-hydroxytryptophan to restore the 5-HT content. However, an increase in 5-HT content of the SCO by pargyline treatment appeared to have no effect on [3H]GABA uptake. Control of GABA uptake activity by 5-HT in the SCO ependymocytes could be an interesting model for the study of a possible interaction between amino-acids and other neurotransmitters by terminating their action in the extracellular space.

Site-dependent central effects of aldosterone in rats.

A relationship between the subcommissural organ (SCO) and the adrenal glands has long been suspected. This report provides further information about the effects of a continuous D-aldosterone infusion into the SCO area of conscious, adult male Sprague-Dawley rats. A 6-day aldosterone infusion (5 ng/h) increased urinary sodium excretion, decreased adrenal medullary cross-sectional area, elevated adrenal corticosterone content and terminal plasma epinephrine concentration. Mineralocorticoid infusions directly into a lateral cerebral ventricle did not affect these parameters but, unlike SCO area infusions, decreased consummatory behavior. Infusions of tritiated aldosterone into the SCO area revealed that radioactivity was mainly confined to dorsomedial portions of the brain near the SCO, whereas the pineal body contained only background radioactivity. The data support the concept that the SCO area interacts with physiological systems related to both the adrenal cortex and medulla.

Morphometric changes in alcoholic mice of neurons of areas 6 and 17 and ependyma of the subcommissural organ.

We have performed a karyometric study of the postnatal development of the subcommissural organ (SOC), the subjacent thalamic ependyma, and the pyramidal neurons of layer V of the motor and visual cortical areas, in alcoholic male albino mice, aged 25-100 days. Ethyl alcohol was added to the drinking water at a concentration of 20%, from birth until the day of sacrifice. Our results show that alcoholism affects the SOC ependyma and the motor cortex, and, apparently, does not affect the ventricular thalamic ependyma and the visual cortex. We suggest a neuroendocrine mechanism to explain the SOC answer, and a functional deprivation to explain the changes in the motor cortex.

Central effects of aldosterone infused into the rat subcommissural organ region.

D-Aldosterone (5 ng/microliter/h) was infused for 6 days into the region of the subcommissural organ (SCO) of conscious, adult male Sprague-Dawley rats. Aldosterone increased urinary sodium loss and the sodium/potassium ratio. Although probably central in origin, these effects still occurred when cannulae were displaced up to 1 mm from the targeted SCO placement. Aldosterone decreased adrenal medullary cross-sectional area without affecting cell density. This effect was highly dependent on proper cannula placement and was not observed when the cannula tip was not in contact with the cerebrospinal fluid of the pineal recess over the rostral two-thirds of the SCO. We conclude that aldosterone increases sodium excretion by an action in the SCO and/or adjacent structures. We also postulate a negative trophic relationship between mineralocorticoids and the adrenal medulla mediated by the SCO.