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D G Standaert

Publications and source records attributed to D G Standaert.

71 records · Page 4Linked to original sources
PubMed1994

Metabotropic glutamate receptor mRNA expression in the basal ganglia of the rat.

Metabotropic glutamate receptors (mGluRs) couple the actions of glutamate to intracellular second messenger systems through G-proteins. The mGluRs play an important role in the regulation of basal ganglia function. Ligand binding studies have revealed that the basal ganglia contain at least two pharmacological types of metabotropic binding sites. Agonists of mGluRs can affect both in vitro electrophysiologic responses of striatal neurons and motor behavior in vivo. Recently, cDNAs encoding five mGluRs have been cloned, each with distinct structural and pharmacological properties. In order to elucidate the function of these receptors in the biology of the extrapyramidal motor system, we have used in situ hybridization to examine the regional and cellular expression patterns of mGluR1-mGluR5 in the adult rat basal ganglia. In the striatum, all of these mGluRs were present in widely varying relative densities and cellular patterns. MGluR5 was particularly prominent, and exhibited a heterogeneous cellular distribution, with labeled and unlabeled populations of neurons. MGluR2 was expressed in a small population of large polygonal striatal neurons. The subthalamic nucleus was the only other basal ganglia structure that expressed mGluR2. Distinct cellular distributions of mGluR expression were also observed within the nucleus accumbens, globus pallidus, ventral pallidum, and substantia nigra pars reticulata. MGluR3 was expressed in glia in all basal ganglia structures, but was observed in neurons only in the striatum, substantia nigra pars reticulata, and very weakly in the subthalamic nucleus. Comparison of the restricted mGluR2 and mGluR3 mRNA distributions with that of metabotropic ligand binding sites supports a possible presynaptic location for these receptors in the basal ganglia. MGluR1 was the only mGluR message prominently expressed in the dopaminergic neurons of the substantia nigra pars compacta, suggesting the involvement of this receptor in the regulation of dopamine release from nigrostriatal terminals.

Animals↗
PubMed1993

Alternatively spliced isoforms of the NMDAR1 glutamate receptor subunit: differential expression in the basal ganglia of the rat.

Several isoforms of the NMDAR1 glutamate receptor subunit are produced by alternative mRNA splicing of three cassette sequences. Using in situ hybridization with exon-specific probes, we have observed differential regional expression of a cassette in the amino terminus of the NMDAR1 subunit, Insertion I, which confers distinct structural and physiologic properties. The differential distribution of expression is most prominent in the basal ganglia, where only the subthalamic nucleus expresses the insertion at high levels.

Animals↗
PubMed1993

Update on the management of Parkinson's disease.

Parkinson's disease is one of the most common neurologic disorders. Recent advances have shed new light on the nature of the disease process and have led to new strategies for management. This article reviews the biology of Parkinson's disease, the diagnostic approach to patients with parkinsonism, pharmacologic treatments, and practical strategies for managing common clinical problems.

Depression↗
PubMed1991

Molecular features of hypothalamic plaques in Alzheimer's disease.

The pathology of Alzheimer's disease (AD) involves subcortical as well as cortical structures. The authors have used immunohistochemical methods to study the molecular composition of AD plaques in the hypothalamus. In contrast to previous studies using histochemical methods, the authors observed large numbers of diffuse plaques in the AD hypothalamus labeled with an antiserum to the beta-amyloid, or A4 peptide, of the beta-amyloid precursor proteins (beta APPs), whereas A4-immunoreactive plaques were uncommon in the hypothalamus of patients without AD. Unlike plaques in the cortex and hippocampus of AD patients, hypothalamic plaques did not contain epitopes corresponding to other regions of the beta APPs, nor did they contain tau-, neurofilament-, or microtubule-associated protein-reactive epitopes, and did not disrupt the neuropil or produce astrogliosis. These findings demonstrate that there are substantial molecular and cellular differences in the pathologic features of AD in the hypothalamus compared with those observed in hippocampal and cortical structures, which may provide insight into the pathogenetic mechanisms of AD.

Aged↗
PubMed1991

Meningovascular syphilis with a gumma of the midbrain.

We report a patient with meningovascular syphilis who had a dorsal midbrain syndrome, cognitive dysfunction, and a left peripheral seventh nerve palsy. Magnetic resonance imaging (MRI) disclosed a large lesion of the midbrain and thalamus with intense enhancement of the interpeduncular cistern, both of which resolved after treatment with intravenous penicillin. The clinical features, radiographic appearance, and response to therapy suggest that this lesion was a focal syphilitic inflammatory process, or gumma. We conclude that MRI with intravenous contrast may reveal the full spectrum of pathologic involvement in neurosyphilis and, in certain situations, may obviate the need for biopsy of an associated mass lesion.

Adult↗
PubMed1988

Expression of the gene for preproatriopeptin in the central nervous system of the rat.

Atriopeptin (AP) is a peptide hormone synthesized and secreted by the atria of the heart that participates in the regulation of fluid and electrolyte balance. AP-like materials have been detected immunologically in neurons in the central nervous system of the rat. In this study, we have used a solution hybridization-nuclease protection assay to determine whether the brain of the rat contains RNA coding preproatriopeptin, the atrial biosynthetic precursor of AP, and to study the regional distribution of preproatriopeptin mRNA in the brain. We have found that the brain contains mRNA identical to the atrial messenger RNA for preproatriopeptin. AP mRNA is differentially distributed in the brain; the highest concentration was found in the hypothalamus, followed by the cortex and septum, hippocampus, midbrain, spinal cord, olfactory bulb, striatum, and pons and medulla. Very low levels were found in the cerebellum, while no detectable AP mRNA was observed in retina, anterior pituitary, or rat liver. The presence of AP mRNA in the brain demonstrates that neurons have the capacity to synthesize preproatriopeptin identical to that produced in the heart. Bioactive peptides produced from this precursor may be endogenous central neuromodulators as well as a circulating hormone.

Animals↗
PubMed1988

Origin of the atriopeptin-like immunoreactive innervation of the paraventricular nucleus of the hypothalamus.

The paraventricular nucleus of the hypothalamus (PVH) contains a prominent collection of varicose atriopeptin-like immunoreactive (APir) fibers. We have used immunohistochemistry and fluorescent retrograde tracers to investigate the origin of these fibers. All parts of the PVH contain APir fibers. The densest collections are found in the periventricular area and in the parvocellular components of the nucleus. Somewhat smaller numbers of fibers are found within the borders of the magnocellular part of the PVH. Following the injection of fluorescent retrograde tracers into the PVH and subsequent immunohistochemical staining, numerous retrogradely labeled APir neurons were observed in the anteroventral periventricular nucleus (AVPV), adjacent to the anteroventral tip of the third ventricle. Smaller groups of retrogradely labeled APir neurons were observed in the ventromedial part of the bed nucleus of the stria terminalis, the pedunculopontine and laterodorsal tegmental nuclei, and the medial part of the nucleus of the solitary tract. The APir projection from the AVPV to the PVH is of particular interest in view of the abundant evidence implicating both regions in the regulation of the fluid and electrolyte balance and blood pressure. AP may serve as a central neuromodulator as well as a circulating hormone in cardiovascular regulation.

Animals↗
PubMed1987

Ventricular atriopeptin. Unmasking of messenger RNA and peptide synthesis by hypertrophy or dexamethasone.

Left ventricular hypertrophy or treatment with dexamethasone caused a 2.5-fold to threefold increase in both immunoreactive atriopeptin (AP) and AP messenger RNA (mRNA), primarily in left ventricular tissue. The combined treatments increased immunoreactive AP and AP mRNA more than either treatment alone. In the animals in which cardiac hypertrophy had been produced by abdominal aortic constriction, there was a decrease in atrial levels of AP and an increase in plasma levels of immunoreactive AP. The increase in left ventricular immunoreactive AP was confirmed by immunohistochemical staining of tissue from hypertrophied and/or dexamethasone-treated rats. The mRNA accumulated in the left ventricle was identical to atrial AP mRNA, as judged by transcriptional start site and by size on Northern blots. Because the mass of ventricular tissue is substantially greater than that of atrial tissue, the induced mRNA levels may represent a total abundance approaching one third of the total AP mRNA in the atria. High performance liquid chromatographic purification of ventricular extracts primarily demonstrated the presence of the high molecular precursor and small amounts of C-terminal peptide AP. Induction of ventricular AP (mRNA and peptide) may represent regression of the tissue to an earlier developmental form. These data provide a unique example of regulation of AP biosynthesis in nonatrial tissue.

Animals↗
PubMed1986

Organization of atriopeptin-like immunoreactive neurons in the central nervous system of the rat.

The atrial natriuretic peptide, atriopeptin, is a circulating hormone that plays an important role in the regulation of fluid and electrolyte homeostasis. Several recent studies have shown that atriopeptin-like immunoreactivity is present within the central nervous system as well as peripheral tissues. In the present report, we describe in detail the organization of atriopeptin-like immunoreactive (APir) perikarya and fibers in the central nervous system of the rat. The most prominent collection of APir perikarya was found in the hypothalamus, adjacent to the anteroventral tip of the third ventricle. Additional groups of APir perikarya were observed along the wall of the third ventricle and in the paraventricular and arcuate nuclei. Separate, smaller groups with distinctive morphology were seen in the lateral hypothalamic area, in the supra-mammillary, medial, and lateral mammillary nuclei, medial habenular nucleus, bed nucleus of the stria terminalis, and the central nucleus of the amygdala. In the pons and brain-stem, APir neurons were observed in the pedunculopontine and laterodorsal tegmental nuclei, as well as in the ventral tegmental area, Barrington's nucleus, the parabrachial nucleus, and the nucleus of the solitary tract. The densest terminal fields of APir fibers were found in the paraventricular nucleus of the hypothalamus, the bed nucleus of the stria terminalis, the median eminence, and the interpeduncular nucleus. The presence of atriopeptin immunoreactivity within the central nervous system suggests that atriopeptin may function as a central neuromediator. Potential functions of this candidate neuromediator deduced from its anatomical distribution are discussed, including the possibility that atriopeptin may function as both a central neuromediator and a systemic hormone in the regulation of the cardiovascular system.

Animals↗
PubMed1986

Colocalization of atriopeptin-like immunoreactivity with choline acetyltransferase- and substance P-like immunoreactivity in the pedunculopontine and laterodorsal tegmental nuclei in the rat.

Atriopeptin, the atrial natriuretic peptide, is a circulating hormone that plays an important role in the regulation of fluid and electrolyte balance. Immunohistochemical studies have shown that large, multipolar atriopeptin-like immunoreactive (APir) neurons are present in areas of the midbrain corresponding to the large neurons of the pedunculopontine tegmental (PPT) and lateral dorsal tegmental (TLD) nuclei, all of which can be stained immunohistochemically for choline acetyltransferase-like immunoreactivity (ChATir). A subpopulation of these cholinergic PPT and TLD neurons are also known to contain substance P-like immunoreactivity (SPir). Using an immunofluorescent technique that allows simultaneous localization of two antigens, we have studied the relationship between APir, SPir and ChATir in the pontine tegmentum of the rat. We have found that the large multipolar APir neurons of the pontine tegmentum are identical to the ChATir neurons of the PT and TLD nuclei and a subpopulation of the APir neurons in PPT and TLD neurons are also SPir.

Animals↗
PubMed1986

Opioid peptide immunoreactivity in spinal and trigeminal dorsal horn neurons projecting to the parabrachial nucleus in the rat.

The parabrachial nucleus (PB) is the major relay for ascending visceral afferent information from the nucleus of the solitary tract to the forebrain. We have recently found that PB in the rat also receives a substantial afferent projection from neurons in the marginal zone of the entire length of the spinal and trigeminal dorsal horn. Immunoreactive perikarya stained with antisera against several neuropeptides--including dynorphin, enkephalins, and substance P--have been identified in the marginal zone. We therefore investigated the chemical specificity of the spinoparabrachial projection by combining fluorescent retrograde tracing with immunofluorescence for substance P, dynorphin A1-17, met-enkephalin, and two enkephalin precursor fragments (proenkephalin 192-203 and peptide E). Following PB injections of fluorescent dyes, about half of the retrogradely labeled neurons in the marginal zone stained with antisera against either dynorphin or enkephalin series peptides. Elution-restaining experiments indicated that the dynorphin- and enkephalin-immunoreactivities were contained within separate populations of marginal zone neurons. We could not identify any substance P-immunoreactive perikarya in the marginal zone, but substance P-immunoreactive fibers were seen in close apposition to retrogradely labeled, opioid-immunoreactive cell bodies and dendrites. These results indicate that the dynorphin- and enkephalin-immunoreactive perikarya in the marginal zone of the dorsal horn represent independent neuronal populations. These opioid-immunoreactive neurons, which are believed to have extensive local collateral connections, are the main source of a long ascending projection to the parabrachial nucleus in the rat. Furthermore, opioid neurons in the marginal zone may receive substance P-immunoreactive primary sensory afferents.

Amidines↗
PubMed1985

Spinal and trigeminal dorsal horn projections to the parabrachial nucleus in the rat.

We studied afferents to the parabrachial nucleus (PB) from the spinal cord and the spinal trigeminal nucleus pars caudalis (SNVc) in the rat by using the anterograde and retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Injections of WGA-HRP into medial PB retrogradely labeled neurons in the promontorium and in lamina I of the dorsal rostral SNVc, while injections into lateral PB and the Kölliker-Fuse nucleus retrogradely labeled neurons in these areas as well as in lamina I throughout the caudal SNVc and spinal dorsal horn. Injections of WGA-HRP into the caudal SNVc and dorsal horn of the spinal cord resulted in terminal labeling in the dorsal, central, and external lateral subnuclei of PB and the Kölliker-Fuse nucleus, all of which are known to receive cardiovascular and respiratory afferent information. Injections of WGA-HRP into the promontorium and dorsal rostral SNVc resulted in terminal labeling in the same PB subnuclei, as well as in the medial and the ventral lateral PB subnuclei, which are sites of relay for gustatory information ascending from the medulla to the forebrain. The spinal and trigeminal projection to PB may mediate the convergence of pain, chemosensory, and temperature sensibilities with gustatory and cardiorespiratory systems in PB.

Afferent Pathways↗
PubMed1985

Atriopeptin-immunoreactive neurons in the brain: presence in cardiovascular regulatory areas.

Antisera to atriopeptin III and to a cyanogen bromide fragment of the precursor molecule atriopeptigen were prepared and used to examine the distribution of atriopeptin-like immunoreactive material in the heart and brain of the rat. Granules of this material were seen in myocytes throughout the right and left atria and were densest in the perinuclear region. The distribution of atriopeptin-like immunoreactive material in the heart is consistent with previous reports of atrial secretory granules. In the brain neurons containing the material were observed in the hypothalamus and the pontine tegmentum. Atriopeptin in the brain may serve as a neurotransmitter in neural systems controlling blood volume and composition, the same physiological functions regulated by blood-borne atriopeptin.

Animals↗
PubMed1984

Proctolin in the lobster: the distribution, release, and chemical characterization of a likely neurohormone.

A radioimmunoassay, immunohistochemical techniques, and high pressure liquid chromatography (HPLC) methods have been developed for the study of the pentapeptide proctolin in the lobster Homarus americanus. Proctolin-like immunoreactivity is present in nearly every portion of the lobster nervous system; immunoreactivity is found in the brain, in each of the ganglia and connectives of the ventral nerve cord, and in many of the nerve roots that emerge from the cord. The greatest amounts are found in the pericardial organs, which are well known neurosecretory structures, and these structures have been selected for more detailed study. The immunoreactive material in the pericardial organs appears to be authentic proctolin. This material co-migrates with synthetic proctolin in two HPLC systems. Furthermore, a peptide that is purified from pericardial organs by HPLC is indistinguishable from synthetic proctolin in high resolution fast atom bombardment mass spectrometry. Cytochemistry reveals that the surface of the pericardial organs is densely covered with immunoreactive varicosities. No cell bodies that stain for proctolin are found in the pericardial organs, and the cells that give rise to the varicosities have not yet been located. The nerve endings in pericardial organs are capable of releasing proctolin-like material when depolarized in the presence of Ca++. These findings suggest that proctolin is a neurohormone in the lobster.

Animals↗
PubMed1977

Beneficial effect of fluorocarbon emulsion media on the function of neuromuscular preparations in vitro.

The effects of liquid fluorocarbons as bathing media were determined by use of in vitro neuromuscular preparations. Rat hemidiaphragms were bathed in either oxygenated fluorocarbon (FC) emulsion or standard oxygenated Krebs solution. Contractile force in response to simple supramaximal nerve stimuli as well as to high frequency stimulation was greater, while twitch:tetanus ratio was smaller in FC emulsion. With such medium, post-tetanic potentiation of contraction was also more consistently observed. Indirectly stimulated diaphragms survived longer in FC emulsion. After cessation of oxygenation, oxygen tension (rhoO(2)) of the medium declined more rapidly with Krebs than with FC emulsion; rhoO(2) directly correlated with force of contraction. Similarly, in the chick biventer cervicis preparation, FC emulsion enhanced nerve-stimulated force of contraction; returning the preparation to standard Krebs solution reversed this phenomenon. Dose-resonse curves of muscle contraction in response to acetycholine and KCl administration were shifted upward during FC emulsion superfusion. Frequency of miniature endplate potentials was lower in FC emulsion than that observed in Krebs solution, measured from the same cell of the rat diaphragm. Resting membrane potentials were also greater in muscle cells sampled from FC emulsion-bathed preparations. These data suggest that FC emulsion is superior to standard Krebs solution as a bathing medium for in vitro neuromuscular preparations by virtue of the high solubility of oxygen in it.

Action Potentials↗
PubMedDate not supplied

Inhibition of the firing of vasopressin neurons by atriopeptin.

Atriopeptin, the atrial natriuretic peptide, is a circulating hormone that is released from the atria of mammalian hearts in response to volume expansion and acts upon the kidneys, adrenal glands and vasculature to regulate fluid and electrolyte homeostasis. Atriopeptin is also present in the brain of the rat. Atriopeptin immunoreactive cell bodies and fibres are found in many areas known to be involved in the central regulation of the cardiovascular system, suggesting that it may be a neuromediator in the central control of fluid and electrolyte balance. The paraventricular nucleus of the hypothalamus, which contains the cell bodies of neurons that secrete vasopressin from the posterior pituitary gland, receives a dense innervation from atriopeptin-like immunoreactive fibres. We have studied the effect of atriopeptin on the electrical activity of single neurons in the paraventricular nucleus of anaesthetized rats and found that atriopeptin is a potent inhibitor of putative vasopressin neurons. Atriopeptin, which has systemic actions that oppose those of vasopressin, may act as a neuromodulator in the brain to prevent vasopressin secretion.

Action Potentials↗