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A P Nicholas

Publications and source records attributed to A P Nicholas.

At least 19 recordsLinked to original sources
PubMed2000

Multiple messengers in descending serotonin neurons: localization and functional implications.

In the present review article we summarize mainly histochemical work dealing with descending bulbospinal serotonin neurons which also express a number of neuropeptides, in particular substance P and thyrotropin releasing hormone. Such neurons have been observed both in rat, cat and monkey, and may preferentially innervate the ventral horns of the spinal cord, whereas the serotonin projections to the dorsal horn seem to lack these coexisting peptides. More recent studies indicate that a small population of medullary raphe serotonin neurons, especially at rostral levels, also synthesize the inhibitory neurotransmitter gamma-amino butyric acid (GABA). Many serotonin neurons contain the glutamate synthesizing enzyme glutaminase and can be labelled with antibodies raised against glutamate, suggesting that one and the same neuron may release several signalling substances, causing a wide spectrum of post- (and pre-) synaptic actions.

Animals↗
PubMed1999

An immunohistochemical investigation of the opioid cell column in lamina X of the male rat lumbosacral spinal cord.

Tri-color immunohistochemistry was employed to examine enkephalin-like immunoreactive neurons in lamina X of the rat lumbosacral spinal cord. Serial coronal sections from levels L1 to S3 were examined. A rostral group of large (40-50 microm diameter), pyramidal-shaped enkephalin-like immunoreactive neurons were shown from levels L1 to L4-5. Essentially all of these neurons were also immunoreactive for galanin and cholecystokinin. A second enkephalin-like immunoreactive cell group, extending from L5 to approximately the S2-3 level, contained smaller (20-30 microm diameter), ovoid-shaped perikaryia. Approximately 75% of these enkephalin-like immunoreactive neurons were also immunoreactive for neuropeptide Y. Neurotensin-immunoreactivity was also present in this area, having varying amounts of co-localization with these other two peptides. These results demonstrate that the lumbosacral opioid cell column in lamina X is not a neurochemically homogenous structure.

Animals↗
PubMed1997

Stiff-persons' syndrome associated with thymoma and subsequent myasthenia gravis.

We report the first case of stiff-persons' (-man) syndrome in the setting of a histologically proven thymoma. Muscular hyperactivity was abolished under general anesthesia and the symptoms of stiffness resolved after thymectomy and three courses of intravenous immunoglobulins. After thymectomy, the patient developed ocular myasthenia gravis which later resolved spontaneously. We suggest that thymoma be sought for in cases with neuromuscular hyperactivity syndromes. Myasthenia gravis may develop subsequently in these cases.

Electromyography↗
PubMed1996

The distribution and significance of CNS adrenoceptors examined with in situ hybridization.

Several of the established alpha 1-, alpha 2- and beta-adrenoceptors have now been isolated and cloned. The in situ hybridization method has been used to map the distribution of many of these adrenoceptors within cells of the CNS. These studies add complementary and new information to our knowledge of adrenoceptor localization provided previously by radioligand-mediated autoradiography. Neuronal cell groups containing one or more mRNAs for seven adrenoceptor subtypes throughout the rat CNS have been mapped. In the present review Anthony Nicholas, Tomas Hökfelt and Vincent Pieribone will examine these localizations and discuss the additional information these maps supply, as well as some implications for understanding central noradrenaline and adrenaline systems.

Animals↗
PubMed1995

Ultrastructural studies on peptides in the dorsal horn of the rat spinal cord--II. Co-existence of galanin with other peptides in local neurons.

Using light microscopic immunoperoxidase and immunofluorescence histochemistry, double-staining methodology, and electron microscopic pre-embedding and post-embedding immunocytochemistry, we studied galanin-immunoreactive neurons in the superficial dorsal horn of the rat spinal cord. Co-existence of galanin with other neuropeptides was also analysed. The lumbar 4 and 5 segments of normal rats and after rhizotomy or spinal cord transection were studied. Galanin-positive local neurons in lamina II were often islet cells and could be classified as type A, which had abundant electron-dense cytoplasm containing many large dense-core vesicles, and type B, which had electron-lucent cytoplasm with only a few large dense-core vesicles. Galanin-positive and -negative peripheral afferent terminals made synaptic contact mostly with galanin-negative dendrites and cell bodies, but also with type B galanin cell bodies and with galanin-positive dendrites of unidentified type. Galanin-immunoreactive terminals from local neurons could also be classified into two types. Type alpha terminals were most common; they contained densely packed synaptic vesicles and many large dense-core vesicles, were strongly immunostained and most frequently made synaptic contact with galanin-negative dendrites. Type beta terminals contained loosely packed synaptic vesicles and a few large dense-core vesicles, and were weakly immunostained. Axosomatic synaptic contact were sometimes found between type beta terminals and type B galanin-positive cell bodies, but were most often associated with galanin-negative dendrites. Double immunostaining showed that galanin-like immunoreactivity co-localized mainly with enkephalin-like, but sometimes also with neuropeptide Y-like immunoreactivity in some local neurons in lamina II. Galanin-like and substance P-like immunoreactivities were identified in the same neurons in deeper layers of the dorsal horn. Coexistence of these neuropeptides and neurotensin with galanin was demonstrated not only in terminals in lamina II but also in large dense-core vesicles, as revealed by post-embedding immunocytochemistry. These results show that galanin-immunoreactive neurons in lamina II receive inputs directly from primary afferents and frequently make synaptic contacts with other intrinsic neurons. Galanin in the superficial dorsal horn may be released both from primary afferents and local neurons to modulate sensory processing in many different ways, including interacting with enkephalin, neuropeptide Y, neurotensin and substance P released from the same and/or other local neurons.

Animals↗
PubMed1994

Distribution of alpha 1 adrenoceptors in rat brain revealed by in situ hybridization experiments utilizing subtype-specific probes.

The distribution of neurons in the rat CNS that synthesize mRNA for the alpha 1A/D and alpha 1B adrenoceptors was revealed by the in situ hybridization method. Forty-eight-mer DNA probes were synthesized to two different and unique regions of both the alpha 1A/D and alpha 1B mRNAs. Tissue sections from all levels of the CNS and some peripheral ganglia were incubated in a hybridization cocktail containing one of these four probes. The two mRNAs were expressed in a discrete and often complementary manner to each other, and identical hybridization patterns were seen for the probes directed against the same mRNA. The alpha 1A/D probes hybridized heavily with neurons in the internal granular and internal plexiform layers of the olfactory bulb, in layers II-V of most areas of the cerebral cortex, and in the lateral aspect of the lateral amygdaloid nucleus, with pyramidal neurons of CA1-CA4 regions, hilar and granular neurons of the dentate gyrus, and neurons in the reticular thalamic nucleus, cranial and spinal motor nuclei, and the inferior olivary nucleus. Light labeling was seen in a variety of other regions in the brain and spinal cord. The alpha 1B probes hybridized heavily with neurons in the mid layers of cerebral cortex and with virtually all neurons in the thalamus, except the reticular and habenular nuclei. In addition, labeling was seen in the lateral and central amygdaloid nuclei, in brainstem and spinal motor nuclei, over most neurons of the dorsal and medullary raphe nuclei and neurons of the intermediolateral cell column in the spinal cord. Light labeling was seen in the septal nucleus, the horizontal limb of the diagonal band, the paraventricular and lateral hypothalamic nuclei, the pontine and medullary reticular formation, and in most laminae in the spinal cord. The patterns of labeling obtained with the alpha 1B probes resemble the labeling seen in previous autoradiographic ligand binding studies utilizing "general" alpha 1 ligands, while the labeling patterns seen with the alpha 1A/D probes do not correspond to any published alpha 1 receptor distribution pattern, indicating that this mRNA likely encodes for a novel adrenoceptor. The present findings further expand the heterogeneity of adrenoceptor mRNAs presented in two accompanying studies (Nicholas et al., 1993a,b). This differential distribution of adrenoceptors subtypes provides a framework for the functional diversity to the apparently widespread, diffuse, and rather homogeneous noradrenergic innervation of the CNS.

Animals↗
PubMed1994

Patterns of messenger RNA expression for adrenergic receptor subtypes in the rat kidney.

The distribution of mRNA for the rat alpha-1 A/D, alpha-1B, alpha-2A/D (RG20), alpha-2B (RNG), alpha-2C (RG10), beta-1 and beta-2 adrenergic receptors were studied in the rat kidney using in situ hybridization. After hybridized sections were exposed to autoradiography film or dipped in photographic emulsion and counterstained with hematoxylin and eosin, specific and selective labeling patterns characteristic for each probe in the kidney were observed. Labeling with the probe to the alpha-1A/D receptor was only observed in vessels in the renal parenchyma and in the ureter. Alpha-1B receptor mRNA was demonstrated in the outer and inner stripe of the outer medulla, corresponding to segment S3 of proximal tubules and the thick ascending limb of loop of Henle. Alpha-2A/D receptor mRNA was distributed in the inner stripe of the outer medulla and in the inner medulla, corresponding to collecting tubules, and in the ureter. The strongest signal in the kidney was obtained with the alpha-2B receptor probe, showing labelling in the outer stripe of the outer medulla with tubular rays radiating into the cortex, coinciding with segment S3 of proximal tubules. Weak labeling obtained with the alpha-2C receptor probe was present in the renal medulla. Labeling obtained with the probe to the beta-1 receptor was seen in the entire cortex and to a lesser extent also in the outer medulla. In addition, beta-1 receptor mRNA was shown in perirenal adipose tissue and in the ureter. Labeling obtained with the probe to the beta-2 receptor was demonstrated in the outer and inner stripe of the outer medulla.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Increased alpha 1B-adrenoreceptor mRNA levels in the rat kidney after thyroidectomy.

Oligonucleotide probes were designed to sequences of the rat alpha 1B- and alpha 2B-adrenergic receptor mRNA and used for in situ hybridization histochemistry on tissue sections of kidneys from control and thyroidectomized rats. Both alpha 1B- and alpha 2B-receptor mRNA labelling was demonstrated in proximal tubule cells in the outer stripe of the outer medulla, with tubular rays radiating into the cortex. Thyroidectomy induced a more than 4-fold increase in mRNA for the alpha 1B-receptor in the kidney, whereas no change in alpha 2B-receptor mRNA levels could be demonstrated in thyroidectomized rats as compared to control animals. The results suggest that thyroid hormone plays an important role in regulating expression of alpha 1B-receptors in renal tubule cells.

Animals↗
PubMed1993

Distributions of mRNAs for alpha-2 adrenergic receptor subtypes in rat brain: an in situ hybridization study.

Selective 35S-labeled oligonucleotide probes were designed to sequences of the rat alpha-2A (RG20), alpha-2B (RNG), and alpha-2C (RG10) adrenoreceptor mRNAs for use in in situ hybridization experiments on sections of unfixed rat brain, spinal cord and kidney. After hybridized sections were exposed to film or dipped in autoradiographic emulsion, specific and selective labeling patterns characteristic for each probe and region of the central nervous system were observed. Alpha-2A mRNA labeling was most pronounced in neurons in layer six of the cerebral cortex, hypothalamic paraventricular nucleus, reticular thalamic nucleus, pontine nuclei, locus coeruleus, vestibular nuclei, trapezoid nuclei, deep cerebellar nuclei, nucleus tractus solitarii, ventrolateral medullary reticular formation, and the intermediolateral cell column of the thoracic spinal cord. In some of these locations, the receptor mRNA, in all probability, is present in noradrenaline and perhaps adrenaline neurons. The alpha-2B probe, which primarily labels the kidney, gave only a very light signal in the thalamus in the central nervous system after extended exposure times. Alpha-2C mRNA labeling was primarily observed in the olfactory bulb, cerebral cortex, islands of Calleja, striatum, hippocampal formation, cerebellar cortex, and dorsal root ganglia. Labeling patterns disappeared when excess unlabeled probes were added to their respective radiolabeled probes, or when sense probes were employed. When a hybrid antisense probe homologous to all three alpha-2 probes was used, labeling patterns also disappeared. The present study therefore justifies the pharmacological subclassification of alpha-2 receptors by providing anatomical evidence for specific and selective cell groups in the rat central nervous system containing mRNA for three alpha-2 receptor subtypes.

Amino Acid Sequence↗
PubMed1993

Ultrastructural studies on peptides in the dorsal horn of the spinal cord--I. Co-existence of galanin with other peptides in primary afferents in normal rats.

The aim of the present study was to investigate galanin-like immunoreactivity in primary afferent terminals and its relationship to other neuropeptides in laminae I and II of the fourth and fifth lumbar segments of normal rat spinal cord using immunofluorescence and pre- and post-embedding electron-microscopic immunocytochemistry. Triple-immunofluorescence staining showed that galanin-like immunoreactivity co-localized with substance P- and calcitonin gene-related peptide-like immunoreactivities in many nerve fibres and terminals in laminae I and II of the dorsal horn. At the ultrastructural level, using pre-embedding immunocytochemistry, galanin-like immunoreactivity was found in type I glomeruli with an electron-dense central terminal containing many densely packed synaptic vesicles and several large dense-core vesicles. Both the cytoplasm and the core of the large vesicles were immunoreactive. In type II glomeruli with an electron-lucent central terminal and loosely packed synaptic vesicles the large dense-core vesicles and the cytoplasm were only weakly galanin-positive. Post-embedding immunocytochemistry revealed that galanin-like immunoreactivity co-existed with substance P- and calcitonin gene-related peptide-like immunoreactivities in many terminals and in individual large dense-core vesicles in lamina II. These terminals were considered to represent primary afferents, since there is evidence that calcitonin gene-related peptide in the dorsal horn only occurs in nerve endings originating in dorsal root ganglia. Evidence was also unexpectedly obtained for the occurrence of several other peptides in calcitonin gene-related peptide-positive terminals, i.e. in presumably primary afferents. Thus galanin-like immunoreactivity sometimes also co-localized with cholecystokinin- and neuropeptide tyrosine-like immunoreactivities in calcitonin gene-related peptide-immunoreactive terminals and in some large dense-core vesicles in such terminals. A small number of calcitonin gene-related peptide immunoreactive, presumably primary afferent terminals contained enkephalin-, neurotensin- (and galanin-)like immunoreactivities. These results indicated that galanin can be co-stored with several other neuropeptides in large dense-core vesicles in primary afferent terminals and may presumably be released together with them in the superficial layer of the dorsal horn. Since various combinations of peptides, presumably at varying concentrations, occur in the large dense-core vesicles in a given nerve ending, it is likely that the individual large dense-core vesicles produced in a neuron are heterogenous with regard to peptide content and thus to the message that they transmit upon release.

Animals↗
PubMed1993

Cellular localization of messenger RNA for beta-1 and beta-2 adrenergic receptors in rat brain: an in situ hybridization study.

Selective, 35S-labeled, oligonucleotide probes were designed from sequences of the rat beta-1 and beta-2 adrenoceptor messenger RNAs for use in situ hybridization experiments on sections of unfixed rat brain and spinal cord. After hybridized sections were exposed to film or dipped in autoradiographic emulsion, specific and selective labeling patterns characteristic for each receptor messenger RNA and region of the central nervous system were observed. For example, labeling for beta-1 messenger RNA was found in the anterior olfactory nucleus, cerebral cortex, lateral intermediate septal nucleus, reticular thalamic nucleus, oculomotor complex, vestibular nuclei, deep cerebellar nuclei, trapezoid nucleus, abducens nucleus, ventrolateral pontine and medullary reticular formations, the intermediate gray matter of the spinal cord and in the pineal gland, while beta-2 messenger RNA labeling was strongest in the olfactory bulb, piriform cortex, hippocampal formation, thalamic intralaminar nuclei and cerebellar cortex. In some of these regions the beta-1 labeling seemed mainly confined to the cell nucleus. Whether or not this apparently nuclear labeling is specific, i.e. indicates synthesis of beta-1 receptor, remains to be established. However, all labeling patterns described disappeared when excess unlabeled probes were added to their respective radiolabeled probes or when sense probes were employed. Since the in situ method labels only cell bodies that produce the messenger RNA for these two beta receptor subtypes, a comparison between these maps and those of past autoradiographic studies mapping the location of central beta receptors using drugs as radioligands may produce further insights regarding the pre- and postsynaptic localization of these receptors in the various parts of the central nervous system circuitry.

Adrenergic Fibers↗
PubMed1992

Serotonin-, substance P- and glutamate/aspartate-like immunoreactivities in medullo-spinal pathways of rat and primate.

Serotonergic neurons of the medulla oblongata have been proposed to play a role in the control of sensory, motor and autonomic cells in the spinal cord. Many of these raphe neurons have been shown to contain the undecapeptide substance P as well as the tripeptide thyrotropin-releasing hormone, but evidence for the presence of an excitatory amino acid in these pathways has not yet been documented. In colchicine-treated rats, we have used a combination of retrograde tracing and tri-color immunohistofluorescence techniques to study co-localization of serotonin- and substance P- with glutamate- or aspartate-like immunoreactivities in medullary neurons and the possible spinal projections of these cells. In addition, the distributions of serotonin-, substance P- and glutamate-immunoreactive terminal fields in the dorsal, ventral and lateral horns of the spinal cord were examined with tri-color immunofluorescence in the rat and the primate Macaca fasciculata. In colchicine-treated rats, glutamate- and aspartate-like immunoreactivity was found in practically all serotonin- and substance P-immunoreactive neurons of the B1, B2 and B3 cell groups. Some of these neurons also contained wheat-germ agglutinin conjugated to inactivated horseradish peroxidase and colloidal gold particles retrogradely transported from the spinal cord. In the spinal cords of non-colchicine-treated monkeys and rats, striking co-localization of serotonin, substance P- and glutamate-like immunoreactivities was seen in large boutons, surrounding the dendrites and cell bodies of large alpha motor neurons in the ventral horn. These observations suggest the existence of spinally projecting serotonin/substance P neurons containing excitatory amino acids such as glutamate or aspartate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Contrasting cardiovascular responses from intrathecal administration of epinephrine and norepinephrine in conscious rats: role of alpha 1- and alpha 2-adrenoceptors.

In conscious rats, intrathecal (i.t.) administration of norepinephrine (NE) produced pressor responses, whereas i.t. epinephrine (Epi) caused depressor responses at low doses (0.1-1 microgram) and pressor responses at a higher dose (10 micrograms). Epi administered i.t. produced bradycardia; however, NE caused tachycardia at low doses and bradycardia at high doses. The cardiovascular responses were dissimilar to those observed after intravenous (i.v.) administration of these doses of NE and Epi. When [3H]NE or [3H]Epi (1.0 microgram, 10 mCi) was injected i.t., minimal radioactivity was detected in peripheral blood (PB) samples, indicating that the effects of i.t.-injected catecholamines on blood pressure (BP) and heart rate (HR) are due to stimulation of central spinal adrenoceptors and not to peripheral effects after leakage. Pretreatment with i.t. administration of the alpha 1-antagonist prazosin (1.0 microgram) attenuated pressor responses and tachycardia produced by i.t. NE (1.0 microgram), whereas i.t. pretreatment with the alpha 2-antagonist yohimbine (10 micrograms) counteracted depressor responses and bradycardia produced by i.t. Epi. Therefore, these spinally released catecholamines appear to produce opposite cardiovascular effects whereby sympathetic preganglionic neurons are excited by NE through spinal alpha 1-adrenoceptors and are inhibited by Epi through spinal alpha 2-adrenoceptors.

Animals↗
PubMed1992

Neuropeptides and classical transmitters. Localization and interaction.

The present article briefly reviews some aspects on the localization and possible functional roles of neuropeptides. It is emphasized that a large number of peptides can be found in the nervous system and that they in many instances occur together with classical transmitters such as acetylcholine and catecholamines in the same neurons. In agreement, functional studies have revealed that they interact in different ways, both synergistically and antagonistically, with the transmitters. In some instances peptides may also have trophic effects. The recent cloning of neuronal peptide receptors has further substantiated a physiological role for these compounds in the nervous system. Moreover, the recent development of peptide antagonists, which pass the blood brain barrier, now opens up new possibilities to elucidate the functional role of neuropeptides and thus of the coexistence phenomenon.

Animals↗
PubMed1991

Projections from the rostral ventrolateral medulla to brainstem monoamine neurons in the rat.

Following the iontophoretic deposition of Phaseolus vulgaris leucoagglutinin (PHA-L) into the rostral ventrolateral medulla (RVL), two-color immunoperoxidase staining was employed to demonstrate contiguity between PHA-L-immunoreactive (PHA-LI) varicose fibers and boutons and brainstem monoaminergic cells. Black-stained PHA-LI cells in the deposition site were found to be located among amber-stained phenylethanolamine N-methyl transferase-immunoreactive (PNMT-I) neurons of the C1 cell group. RVL projections were contiguous with PNMT-I neurons of the C1, C2 and C3 cell groups, with tyrosine hydroxylase-immunoreactive (TH-I) neurons of the A1, A2 and A5 cell groups, and with serotonin-immunoreactive (5-HT-I) neurons of the B1, B2 and B3 cell groups. Preliminary findings of this study have been presented previously (Soc. Neurosci. Abstr., 15 (1989) 451).

Animals↗
PubMed1990

Evidence for projections from the rostral medullary raphe onto medullary catecholamine neurons in the rat.

Following the iontophoretic deposition of Phaseolus vulgaris leucoagglutinin (PHA-L) into the rostral medullary raphe, which included portions of the caudal nucleus raphe magnus, rostral nucleus raphe pallidus, rostral nucleus raphe obscurus and rostral nucleus reticularis paragigantocellularis, two-color immunoperoxidase staining was employed to demonstrate contiguity between PHA-L-immunoreactive (PHA-LI) varicose fibers and boutons and medullary catecholamine (CA) cells. Raphe projections were contiguous with phenylethanolamine N-methyltransferase-immunoreactive (PNMTI) neurons in the C1, C2 and C3 cell groups and with tyrosine hydroxylase-immunoreactive (THI) neurons in the A1 and A2 cell groups. Contiguity between PHA-LI processes and medullary CA cells was observed most frequently in the C1 cell group. Preliminary findings of this study have been presented previously.

Animals↗