Showing papers on "Area postrema published in 1994"

Spatially and temporally differentiated patterns of c-fos expression in brainstem catecholaminergic cell groups induced by cardiovascular challenges in the rat.

Abstract: Brainstem catecholaminergic neurons have been implicated as mediating adaptive autonomic and neuroendocrine responses to cardiovascular challenges. To clarify the nature of this involvement, immuno- and hybridization histochemical methods were used to follow c-fos expression in these neurons in response to acute stimuli that differentially affect blood pressure and volume. From low basal levels, hypotensive hemorrhage (15%) provoked a progressive increase in the number and distribution of Fos-immunoreactive (ir) nuclei in the nucleus of the solitary tract (NTS), the A1 and C1 cell groups of the ventrolateral medulla, and in the pontine A5, locus coeruleus, and lateral parabrachial cell groups peaking at 2.0-2.5 hours after the challenge. Fos-ir ventrolateral medullary neurons, subsets of which were identified as projecting to the paraventricular hypothalamic nucleus or spinal cord, were predominantly aminergic, whereas most of those in the NTS were not. Infusion of an angiotensin II antagonist blunted hemorrhage-induced Fos expression in the area postrema, and attenuated that seen elsewhere in the medulla and pons. Nitroprusside-induced isovolemic hypotension yielded a pattern of c-fos induction similar to that seen following hemorrhage, except in the area postrema and the A1 cell group, where the response was muted or lacking. Phenylephrine-induced hypertension stimulated a restricted pattern of c-fos expression, largely limited to induced hypertension stimulated a restricted pattern of c-fos expression, largely limited to non-aminergic neurons, whose distribution in the NTS conformed to the termination patterns of primary baroreceptor afferents, and in the ventrolateral medulla overlapped in part with those of vagal cardiomotor and depressor neurons. These findings underscore the importance of brainstem catecholaminergic neurons in effecting integrated homeostatic responses to cardiovascular challenges and their ability to responding strategically to specific modalities of cardiovascular information. They also foster testable predictions as to effector neuron populations that might be recruited to respond to perturbations in individual circulatory parameters.

Regional induction of tumor necrosis factor alpha expression in the mouse brain after systemic lipopolysaccharide administration

Abstract: Tumor necrosis factor alpha (TNF-alpha) is a cytokine that is responsible, in part, for several aspects of the acute-phase response to inflammation, including the generation of fever. TNF-alpha has direct effects on central nervous system neurons deep within the hypothalamus that are involved in producing the febrile response, but the blood-brain barrier prevents circulating TNF-alpha from having access to these sites. We therefore have hypothesized that TNF-alpha may be produced in the brain and used as a mediator in the cerebral components of the acute-phase response. We used in situ hybridization to determine the distribution of production of TNF-alpha mRNA in the mouse brain after systemic administration of lipopolysaccharide. During the initial phase of fever, hybridization was observed in perivascular cells and neurons in circumventricular organs, including the vascular organ of the lamina terminalis, median eminence, and area postrema, as well as along the ventral surface of the medulla; hybridization was also prominent over many cell in the meninges. During the late phase of the response, hybridization was observed over neurons in the pericircumventricular nuclei such as the anteroventral periventricular and arcuate nuclei of the hypothalamus and the nucleus of the solitary tract. TNF-alpha produced by a cascade of neurons within the brain may participate in the complex autonomic, neuroendocrine, metabolic, and behavioral responses to infection and inflammation.

Systemic interleukin-1 induces early and late patterns of c-fos mRNA expression in brain.

Abstract: This study was designed to examine the mechanisms by which systemic interleukin-1 affects neuroendocrine systems in the brain. Intraperitoneal injections of interleukin-1 beta (1.25 micrograms/rat) were administered to rats. One or three hours after injection, the expression levels of the immediate-early gene c-fos and of genes for several neuropeptides, receptors, and enzymes were examined by in situ hybridization histochemistry. In the brainstem at 1 hr, c-fos mRNA was elevated in the area postrema and nucleus of the solitary tract, but not in the locus coeruleus. At 3 hr, the c-fos mRNA levels had increased further in the nucleus of the solitary tract. Rostrally, elevations in c-fos mRNA levels were found in the hypothalamic and thalamic paraventricular nuclei, central nucleus of amygdala, bed nucleus of the stria terminalis, and medial preoptic area, peaking at 1 hr and diminishing at 3 hr. In addition, at 3 hr a new pattern of c-fos activity emerged--the arcuate nucleus and cells at the external margins throughout the brain now expressed c-fos mRNA. Corticotropin-releasing hormone mRNA levels were doubled in the paraventricular nucleus at 1 and 3 hr, concomitant with elevations in plasma adrenocorticotrophic hormone (ACTH) and corticosterone. Tyrosine hydroxylase mRNA levels in the brainstem did not change. The c-fos mRNA induction patterns reveal a temporally dynamic response to interleukin-1 administration. We propose that the early set of structures responding to interleukin-1 initiates the neuroendocrine response to cytokines. Coactivation of the area postrema and nucleus of the solitary tract may reflect entry into the brain and neural transduction of the peripheral signal. The late set--including the nucleus of the solitary tract, arcuate nucleus, and the brain's edge--may reflect cellular activation along the diffusion routes traveled by interleukin-1 or a bioactive transduction product, because the pattern of edge labeling is similar to the autoradiographic pattern of flow lf radiolabeled tracer substances in the cerebrospinal fluid. The late c-fos mRNA response to interleukin-1, therefore, may represent a demonstration of information transfer in the parasynaptic mode, also known as volume transmission.

Emetic reflex arc revealed by expression of the immediate-early gene c- fos in the cat

Abstract: The organization of the central neuronal circuitry that produces vomiting was explored by mapping the distribution of c-fos protein (Fos)-like immunoreactivity (FLI) as a monitor of functional activity The brainstem and spinal cord were examined in cats administered multiple emetic drugs (cisplatin, lobeline, protoveratrine, naloxone, apomorphine) or control saline injections Some animals were decerebrated, paralyzed, and artificially ventilated to avoid possible Fos expression induced by sensory feedback or fluid depletion during vomiting Fictive vomiting was identified in these animals by a characteristic pattern of respiratory muscle nerve (phrenic and abdominal) coactivation Tissues were immunoprocessed using an antibody raised against amino acids 1-131 of Fos and the avidin-biotin peroxidase complex method Enhanced nuclear FLI was observed in experimental animals along portions of the sensorimotor emetic reflex arc, including the nodose ganglia, area postrema, nuclei of the solitary tract (especially medial and subpostrema subnuclei), intermediate reticular zone of the lateral tegmental field, nucleus retroambiguus, C2 inspiratory propriospinal cell region, and dorsal vagal and phrenic motor nuclei Enhanced FLI was also detected in the raphe magnus, subretrofacial nucleus, and spinal dorsal horn Regions showing no recognizable differences in FLI between experimental and control animals included the vestibular, cochlear, spinal trigeminal, subtrigeminal, and lateral reticular nuclei Only minor differences were observed in the distributions of FLI between intact and decerebrate animals No unique, well-defined group of labeled neurons that might function as a "vomiting center" could be identified Instead, the pattern of c-fos expression suggests that neurons involved in coordinating the emetic response may radiate from the area postrema and nucleus of the solitary tract to an arc in the lateral tegmental field implicated in somato-autonomic integration

Neuroexcitatory and neurotoxic actions of the amnesic shellfish poison, domoic acid.

Abstract: We have investigated the action of domoic acid in the mouse brain following systemic exposure. Domoic acid increased c-fos mRNA within 15 min and its translational product (c-Fos) within 1 h. c-Fos immunoreactivity was most prominent in the hippocampal formation, lateral septal nucleus, olfactory bulb, area postrema and the nucleus of the solitary tract. We next examined irreversible toxic effects of domoic acid. Domoic acid caused extensive degeneration in CA1-2 of the hippocampus, lateral septal nucleus and olfactory bulb. No degeneration was evident in the dentate gyrus or brain stem. These studies demonstrate that domoic acid has only neuroexcitatory effects on brain stem regions associated with visceral function whereas it has permanent neurotoxic effects on brain regions associated with memory formation.

Expression of c-fos protein in rat brain elicited by electrical and chemical stimulation of the hypothalamic paraventricular nucleus.

Abstract: The functional connectivity of the paraventricular nucleus of the hypothalamus (PVN) was studied by assessing the expression of the immediate early gene, c-fos, after unilateral stimulation of this structure in urethane-anesthetized rats. Electrical stimulation for 1 h (10 s on, 10 s off; 15-40 µA at 20 Hz) was accompanied by increases in mean arterial pressure (13-29 mm Hg). In these animals, ipsilateral increases in numbers of neurons with Fos-like immunoreactivity (FLI) were immunohistochemically demonstrated in the insular cortex, lateral septum, medial amygdala, hypothalamus, lateral division of the parabrachial nucleus (PBN) of the pons and the nucleus of the tractus solitarius (NTS) and ventrolateral medulla (VLM). Numbers of cells with FLI were quantitated in five areas known for their roles in autonomic function: arcuate nucleus, ventromedial hypothalamus, lateral PBN, NTS (at three levels) and VLM (caudal and rostral). In each case, stimulation of the PVN led to significant differences in number of neurons with FLI on the side ipsilateral to the stimulation compared to the contralateral side. To eliminate effects associated with stimulation of fibers of passage in the vicinity of the PVN, the results after electrical stimulation were compared to those obtained in animals in which the PVN was chemically stimulated unilaterally with the excitatory amino acid L-glutamate (5 one-minute infusions of 50 nl, 0.5 M glutamate over 1 h). Mean arterial pressure was increased after each injection (7–13 mm Hg), and significant differences in numbers of neurons with FLI between sides were maintained in all five areas except the NTS caudal to, and at, the level of the area postrema. An increase in neurons with FLI in the piriform cortex of all animals including controls may be due to injury-induced activation of target neurons from the PVN. These data illustrate that electrical and chemical stimulation of the PVN leads to simultaneous activation of neurons in many targets. All of the target areas studied receive direct projections from the PVN, although multisynaptic projections may also contribute to activation of target neurons.

Fos expression in ferret dorsal vagal complex after peripheral emetic stimuli

Abstract: The aim of this study was to investigate neuronal activation in the dorsal vagal complex of the halothane-anesthetized ferret after peripheral emetic stimuli. Neuronal activity was studied by examining the distribution of the nuclear phosphoprotein Fos using immunohistochemistry. The emetic stimuli used were electrical stimulation of the supradiaphragmatic vagal communicating branch (SVCB) or intraduodenal injection of hypertonic saline. Electrical stimulation of the SVCB induced the densest Fos expression within the medial subnucleus of the nucleus of the solitary tract. After hypertonic saline injection, the greatest density of Fos-positive nuclei was observed within the area postrema and also in the medial subnucleus of the nucleus of the solitary tract. It was concluded that the emetic response to hypertonic saline involves neurons in both the area postrema and the nucleus of the solitary tract, especially the medial subnucleus, and that the medial subnucleus is important in the emetic response to SVCB stimulation.

Effects of gastric distension and electrical stimulation of dorsomedial medulla on neurons in parabrachial nucleus of rats.

Abstract: The effects of gastric distension and electrical stimulation of the dorsomedial medulla on neurons within the parabrachial nucleus (PB) were investigated electrophysiologically in urethane-chloralose anesthetized rats. Among 74 neurons tested, electrical stimulation of the nucleus of the solitary tract (NTS) excited 30 neurons (excitatory neurons) and inhibited 14 neurons (inhibitory neurons). Fourteen neurons increased and 12 neurons decreased their discharge rates in response to gastric distension. Twenty-two neurons responded to both electrical stimulation of the NTS and gastric distension. Both excitatory and inhibitory neurons showed either an increase or a decrease in discharge rate responding to gastric distension. Furthermore, three neurons that decreased their discharge rates and two neurons that increased their discharge rates during gastric distension also responded to intravenous administration of metaraminol indicating some effect of baroreceptor activation on the neural activity. The responses of another 49 neurons in the PB to electrical stimulation of area postrema and gastric distension were analyzed. Electrical stimulation of the AP excited 14 neurons and inhibited only one neuron. Five neurons increased and seven neurons decreased their discharge rates in response to gastric distension. Only one inhibitory neuron responded to gastric distension. These observations suggested that the PB neurons received gastric mechanoreceptive inputs from the NTS.

A hypotensive and bradycardic action of gamma 2-melanocyte-stimulating hormone (gamma 2-MSH) microinjected into the nucleus tractus solitarii of the rat.

Abstract: In conscious and urethane-anesthetized rats intravenously (i.v.) administered γ2-melanocyte-stimulating hormone (γ2-MSH), a melanotropin derived from the precursor peptide pro-opiomelanocortin (POMC), has been shown to induce a pressor response combined with a tachycardia. A site of action within the hindbrain, e.g. the nucleus tractus solitarii (NTS) or the area postrema (AP), has been suggested.

Quantitative localization of angiotensin II receptor subtypes in spontaneously hypertensive rats

Abstract: Angiotensin II (Ang II) receptors were labelled by in vitro autoradiography using 125I-[Sar1,Ile8]Ang II as a ligand in the kidney, adrenal gland, thoracic aorta, and hindbrain of adult spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Ang II receptors were differentiated into subtypes by susceptibility to subtype 1 (AT1) and subtype 2 (AT2) antagonists. In both rat strains, the adrenal cortex contained predominantly AT1 receptors, while AT2 receptors predominated in the adrenal medulla. The kidney contained exclusively AT1 receptors in glomeruli, proximal tubules, and the outer medulla. AT1 receptors were predominant in the thoracic aorta. The nucleus of the solitary tract (NTS), dorsal motor nucleus of the vagus (DM10), area postrema, and spinal trigeminal nucleus (Sp5) contained exclusively AT1 receptors, whereas the nucleus of the inferior olive contained AT2 receptors predominantly. Significant differences in receptor density were observed between SHR and WKY. The adrenal cortex, renal outer medulla, NTS, DM10, and Sp5 displayed higher AT1 receptor density in SHR than in WKY. These results indicate that expression of AT1 receptors is regulated differently in important targets of Ang II in SHR, and suggest that altered regulation of AT1 receptor expression may be relevant to the pathogenesis of hypertension in SHR.

Deoxynivalenol (Vomitoxin)-Induced Conditioned Taste Aversions in Rats Are Mediated by the Chemosensitive Area Postrema

Abstract: The present experiments used a conditioned aversion to a novel saccharin taste to assess the aversive effects of deoxynivalenol (vomitoxin) administration, and to examine the putative mediating role of the chemosensitive area postrema (AP). In experiment 1 adult male rats drank a novel 0.15% saccharin solution followed by injection of deoxynivalenol (n = 7; 0.125 mg/kg, IP) or vehicle (n = 7; propylene glycol, 0.5 mg/kg). In subsequent two-bottle preference tests the rats conditioned with deoxynivalenol displayed significantly (p < 0.01) lower absolute and relative saccharin intake levels in comparison to control rats which exhibited a strong preference for saccharin solution. In experiment 2 adult male rats received area postrema ablations (n = 6) or sham lesions (n = 6). On two conditioning days all rats drank a novel 0.15% saccaharin solution followed by injections of deoxynivalenol (0.125 mg/kg, IP). In subsequent two-bottle preference tests the sham-lesioned rats displayed a significant (p < 0.01) aversion to the saccharin stimulus, relative to the area postrema-ablated rats which exhibited a preference for the saccharin solution. Thus, systemic administration of deoxynivalenol, following a novel taste, induced conditioned taste aversions which were mediated by the area postrema.

Cardiovascular effects of angiotensin III in brainstem nuclei of normotensive and hypertensive rats.

Abstract: The cardiovascular role of angiotensin III (ANG III) in the central nervous system is unclear. In this study, we investigated the hemodynamic effects of microinjection of ANG III and compared them with those of angiotensin II (ANG II) into the cerebral ventricle (i.c.v.), the area postrema (AP) and the nucleus tractus solitarii (NTS) of urethane-anesthetized rats. Male Sprague-Dawley rats [normal, renovascular hypertensive (2-kidney, 1-clip) and sham-operated groups] were used in this study. A dose-dependent pressor and bradycardic effect of ANG II and ANG III was observed after i.c.v. injection. When low doses of ANG II or ANG III were microinjected into both NTS and AP, a dose-dependent depressor and bradycardic effect were observed. The maximal depressor effect was observed at 9.6 pmol. When we increased the doses of ANG II or ANG III into the NTS, a pressor and tachycardic effect were observed. A significant difference of the cardiovascular effects of ANG III were noticed between renovascular hypertensive rats and sham-operated rats. The sympathetic nerve activity was inhibited by both pressor and depressor effects. The cardiovascular actions of both ANG II and ANG III were partially or completely abolished after pretreatment of their selective antagonists. These results indicate that the pressor effect of i.c.v. angiotensin are not mediated by activations of angiotensin receptors in the NTS or in the AP.