Biomedical subjects

S R Vincent

Publications and source records attributed to S R Vincent.

At least 73 records · Page 4Linked to original sources

PubMed1989

Cerebral histamine levels are unaffected by MPTP administration in the mouse.

The mechanism by which 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) depletes forebrain dopamine is not fully understood, but a necessary step involves the formation of neurotoxic MPP+ by monoamine oxidase type B (MAO-B). The histamine neurons in the brain contain MAO-B and are a possible site for the production of MPP+. Two weeks after MPTP injections (2 X 50 mg/kg i.p.) in C-57 mice, striatal dopamine was reduced by more than 70%. However, histamine levels in neocortex, hippocampus and hypothalamus were unaffected by this neurotoxic dose of MPTP. Thus, as in Parkinson's disease, central histaminergic systems appear to be spared in the MPTP model.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1989

Effects of short- and long-term haloperidol administration and withdrawal on regional brain cholecystokinin and neurotensin concentrations in the rat.

The effects of oral administration of the neuroleptic, haloperidol, on regional brain concentrations of cholecystokinin (CCK) and neurotensin were examined in the rat. Both short-term (3 weeks) and long-term (8 months) haloperidol administration increased the concentration of CCK in the substantia nigra. While short-term administration significantly increased the concentration of CCK in the ventral tegmental area and decreased the concentration of CCK in the cortex, including the medial prefrontal cortex, these effects were not observed following long-term drug administration. In contrast, long-term, but not short-term, haloperidol administration decreased the concentration of CCK in the olfactory tubercle. Withdrawal from long-term haloperidol did not alter CCK concentrations in any of the brain regions examined. Short-term haloperidol administration significantly increased the concentration of neurotensin in the caudate-putamen. Both short- and long-term administration increased the concentration of neurotensin in the nucleus accumbens, but only the increased following long-term administration reached statistical significance. Withdrawal from long-term haloperidol administration slightly decreased the concentrations of neurotensin in the caudate-putamen and nucleus accumbens. These results indicate that dopamine receptor blockade can affect both CCK- and neurotensin-containing neural systems. Furthermore, these two neuropeptides are affected differently depending upon the duration of haloperidol administration and withdrawal from this drug. The results raise the possibility that chronic administration of haloperidol may be toxic to some neurotensin-containing neurons in the basal ganglia.

Administration, Oral↗

PubMed1989

Distribution of reduced-nicotinamide-adenine-dinucleotide-phosphate diaphorase-positive cells and fibers in the cat central nervous system.

Previous histochemical studies have suggested that reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase exists in distinct subsets of neurons that neither belong to a single transmitter type nor embrace all the neurons using a single transmitter. As a step toward establishing the role of this enzyme, the distribution of NADPH-diaphorase-positive neurons and fibers in the cat central nervous system was mapped by using a direct histochemical method. Heavily stained NADPH-diaphorase-positive neurons with many prominent cell processes were observed in the cerebral cortex, white matter, caudate nucleus, putamen, nucleus accumbens, septal nucleus, amygdala, anterior, lateral and posterior hypothalamic areas, dorsolateral part of the periaqueductal gray, superior colliculus, central tegmental field (Berman) (pedunculopontine tegmental area), dorsal tegmental nucleus, nucleus coeruleus, mesencephalic and pontine reticular formation, gigantocellular and magnocellular tegmental fields, nucleus facialis, and motor nucleus of the vagus. Moderately stained neurons with two or three prominent cell processes were observed in the nucleus of the diagonal band of Broca, globus pallidus, and substantia innominata. Medium-size, moderately stained neurons that had round large nuclei and no visible cell processes were found in the subthalamic nucleus, pontine gray, trapezoid body, and infratrigeminal, cochlear, and vestibular nuclei. Very dense NADPH-diaphorase-positive nerve terminal fields were seen in the olfactory tubercle, cortex, caudate nucleus, putamen, dentate gyrus, and interpeduncular nucleus. Intensely stained NADPH-diaphorase-positive nerve fibers were found in the stria terminalis, marginal region of the central tegmental field, dorsal tegmental nucleus, and spinal trigeminal tract as well as around the brachium conjunctivum. Although the staining of neurons and tracts was highly selective, they did not correspond to any single known neuronal or neurotransmitter type. Positive staining occurred in discrete subsets of neurons known to be associated with a variety of peptides and classical neurotransmitters. The functional significance of high NADPH diaphorase activity is unknown.

Animals↗

PubMed1989

A heavy metal marker of the developing striatal mosaic.

The pattern of distribution of heavy metals in the developing rat striatum was examined using the sulphide silver histochemical method of Timm. The staining was very weak on postnatal day 3 but by day 6 was found in distinct patches. The staining had assumed a fairly homogeneous distribution by day 11 similar to that seen in the adult. This appeared to be due to an increased staining in the matrix, rather than a reduction in the patches, some of which could still be discerned even in the adult. The Timm-stained patches present on day 6 corresponded to the tyrosine hydroxylase immunoreactive patches which have been previously described in the developing striatum. Since zinc appears to be the principal metal detected by the Timm method in brain, the Timm staining pattern seen in the present study may be related to a zinc-growth factor complex in the developing striatum.

Aging↗

PubMed1989

Histochemical localization of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine oxidation in the mouse brain.

The sites in the mouse brain where 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine can be oxidized to the toxic metabolite 1-methyl-4-phenylpyridine were determined using a histochemical technique. The method involved the demonstration of monoamine oxidase activity using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine as the substrate by means of a sensitive coupled peroxidase technique. The distribution of neurons displaying the ability to oxidize 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine via a monoamine oxidase catalysed reaction was compared to that of various amine systems identified with immunohistochemistry. Dopamine neurons, and in particular the nigrostriatal dopamine cells, did not display the capacity to oxidize 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Noradrenergic neurons showed intense monoamine oxidase activity when 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine was used as substrate, and this activity was blocked by the monoamine oxidase-A inhibitor clorgyline. Serotonin neurons and histamine neurons were also able to oxidize 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The reaction in these neurons was blocked by deprenyl, an inhibitor of monoamine oxidase-B. Pretreatment with inhibitors of monoamine oxidase-B has been previously shown to prevent the neurotoxic action of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on dopaminergic neurons. Therefore, since serotonin and histamine neurons are able to oxidize 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by means of monoamine oxidase-B, these neurons may be involved in the production of the toxic metabolites of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in vivo.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1989

Histochemical characterization of neuronal NADPH-diaphorase.

We examined the properties of neuronal NADPH-diaphorase in sections of rat striatum, using histochemical procedures. NADPH-diaphorase histochemistry stained discrete populations of central neurons and provided a Golgi-like image of the neurons exhibiting this activity. The NADPH-diaphorase reaction appeared to be enzyme catalyzed, since it was abolished by pre-treatment with proteases, heat, and acid or alkaline denaturation. Under anaerobic conditions, any tetrazolium salt with a redox potential more positive than NADPH could be reduced by the enzyme. NADPH-diaphorase activity was sensitive to inhibition by sulfhydryl reagents but was unaffected by metal chelators, superoxide dismutase, and catalase. Therefore, the enzyme is unlikely to be a metalloenzyme or to reduce tetrazoliums by producing superoxide anions or hydrogen peroxide. Various analogues of beta-NADPH could be used by the enzyme; however, beta-NADH, which can be used by DT-diaphorase, was ineffective. The enzyme was also resistant to dicumarol, an inhibitor of DT-diaphorase activity. Electron microscopy indicated that the NADPH-diaphorase reaction resulted in staining of various membranous organelles. We conclude that neuronal NADPH-diaphorase is a membrane-bound enzyme distinct from DT-diaphorase and other known enzymes with diaphorase activity. The histochemical characteristics presented here should now enable meaningful biochemical studies of neuronal NADPH-diaphorase to be undertaken.

Animals↗

PubMed1988

Reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase-positive neurons in cat cerebral white matter.

Two populations of neurons in the cat cerebral white matter were detected using histochemistry for reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase activity. One type was bipolar in shape with two cell processes extending in opposite directions, existed mainly in the subcortical areas and was oriented parallel to fiber bundles. The second type had 4 or 5 very long, prominent and varicose cell processes radiating in various directions. They were round or polygonal in shape and formed networks in the white matter of the frontoparietal area. NADPH-diaphorase-positive neurons were also examined by the modified Golgi-Cox silver impregnation method. With this impregnation method, the same two morphological types could be detected but the detailed morphology of these particular populations of neurons was revealed much more fully by NADPH-diaphorase enzyme histochemistry than by the silver impregnation method.

Animals↗

PubMed1988

A population of very small striatal neurons in the cat displays vasoactive intestinal polypeptide immunoreactivity.

Cells displaying vasoactive intestinal polypeptide (VIP) immunoreactivity were demonstrated in the feline striatum using a monoclonal antibody raised against natural porcine VIP. The VIP-immunoreactive neurons in the cat striatum were very small, (8 microns diameter) bipolar and multipolar cells. The VIP-positive neurons were more numerous than the cholinergic neurons but less common than the somatostatin-immunoreactive cells in the cat caudate-putamen. The VIP-immunoreactive cells were localized predominantly in the striatal matrix and tended to avoid enkephalin-immunoreactive patches. Thus VIP-immunoreactive cells comprise another neurochemically defined neuronal population which appears to observe striosomal organization.

Animals↗

PubMed1988

Ultrastructure of reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase-positive neurons in the cat cerebral cortex, amygdala and caudate nucleus.

The ultrastructure of reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase-positive neurons in cat cerebral cortex, amygdala and caudate nucleus was investigated by electron microscopy using a modified method applicable to aldehyde-fixed tissues. These NADPH diaphorase-positive neurons were morphologically similar to neurons immunohistochemically positive for somatostatin. They had large amounts of electron-dense formazan reaction products scattered through the whole cytoplasm but not in the mitochondria or nucleus. Similar electron-dense reaction products were visible in the dendrites of these neurons. The results indicate that NADPH diaphorase histochemistry is a useful method for the ultrastructural examination of particular groups of neurons.

Amygdala↗

PubMed1988

Methylmercury-induced movement and postural disorders in developing rat: loss of somatostatin-immunoreactive interneurons in the striatum.

Tissue concentrations of the neuropeptide somatostatin and the specific activities of glutamic acid decarboxylase (GAD) were measured in several regions of the central nervous system in young rats, following chronic postnatal administration of methylmercuric chloride. By the beginning of the fourth postnatal week, these animals exhibited clinical signs of a mixed spastic/dyskinetic syndrome with visual deficits. At the onset of neurological impairment, a significant decrease in GAD activity was detected in the occipital cortex (48-49%) and striatum (45-50%) when compared to either normal or weight-matched controls. At one subclinical stage of toxicity, decreased GAD activity was detected only in the occipital cortex (29-30%). Tissue levels of somatostatin did not change significantly in the occipital cortex of methylmercury-treated animals at any stage of the experiment. However, somatostatin levels in the striatum were significantly reduced at the onset of neurological impairment (55-57%) and at one subclinical stage of toxicity (49-54%). Immunohistochemistry for somatostatin- and neuropeptide Y-immunoreactive neurons confirmed a marked loss of cells in the dorsolateral region of the striatum with atrophy of the surviving neurons. In the cerebral cortex of methylmercury-treated animals the morphology and distribution of somatostatin-positive neurons appeared normal. In view of the reported co-localization of GAD and somatostatin in some non-pyramidal neurons of the cerebral cortex, these results indicate that methylmercury-induced lesions of the developing cerebral cortex involve a subpopulation of GABAergic neurons which are not co-localized with somatostatin. In the striatum, where GAD and somatostatin are not co-localized within the same neurons, methylmercury-induced lesions involve both GABAergic and somatostatin-positive neurons.

Aging↗

PubMed1988

Comparison between short- and long-term haloperidol administration on somatostatin and substance P concentrations in the rat brain.

Neuroleptics influence a variety of putative neurotransmitters in the basal ganglia, including somatostatin and substance P. Most studies have been performed in animals after only 3 or 4 weeks of neuroleptic administration and have seldom examined the effects of withdrawal. To understand better the effects of haloperidol on neuropeptide systems, the effects of short-term (3 weeks) and long-term (8 months) administration, as well as withdrawal from long-term administration of haloperidol, on somatostatin and substance P concentrations were examined in the rat. Short-term haloperidol significantly decreased the concentrations of somatostatin in the caudate-putamen, nucleus accumbens, and ventral tegmental area, and decreased the concentration of substance P in the substantia nigra and the nucleus accumbens. However, long-term administration only decreased the concentration of somatostatin in the nucleus accumbens. In addition, a slight reduction in the concentration of substance P in the medial prefrontal cortex was detected after long-term treatment. After withdrawal from long-term haloperidol administration the concentrations of these peptides did not differ from control values in any of the brain regions examined. These results confirm that dopamine receptor blockade can affect the somatostatin and substance P systems in the basal ganglia and indicate that during long-term administration (8 months) tolerance develops to some of the effects that are observed after shorter (3 weeks) treatment periods.

Animals↗

PubMed1988

Distributions of tyrosine hydroxylase-, dopamine-beta-hydroxylase-, and phenylethanolamine-N-methyltransferase-immunoreactive neurons in the brain of the hamster (Mesocricetus auratus).

Antibodies to the catecholamine synthetic enzymes tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), and phenylethanolamine-N-methyltransferase (PNMT) were used in an immunohistochemical analysis of the brain of the golden hamster. The distributions and morphological characteristics of neurons displaying immunoreactivity to these enzymes were examined in sets of adjacent sections. Various novel groups of TH-immunoreactive neurons were found. A distinct feature observed in the hamster brain was the presence of a population of magnocellular multipolar neurons in the basal forebrain which displayed intense TH immunoreactivity. These cells were found predominantly in the vertical and horizontal limbs of the nucleus of the diagonal band of Broca and in the lateral preoptic area. Many small TH-positive cells were also found scattered in the deeper layers of the cortex in the hamster. The pericentral divisions of the inferior colliculus contained a large number of TH-immunoreactive neurons, and a few small bipolar cells in the lateral superior olive were also stained. A major cell group was found in the lateral parabrachial nucleus at the level of the locus ceruleus that displayed TH but not DBH immunoreactivity and was obviously separate from the TH- and DBH-positive cells of the locus ceruleus. Additional TH-positive cell groups were found along the seventh nerve, within the medial longitudinal fasiculus, in the nucleus raphe pallidus, and in the pars caudalis of the spinal trigeminal nucleus. The various catecholamine cell groups described by many people in the rat by use of histochemical and immunohistochemical techniques were also present in the hamster brain. These included the noradrenergic, TH- and DBH-immunoreactive cell groups of the pons and medulla. The hamster also displayed groups of medullary neurons displaying immunoreactivity to TH, DBH, and PNMT. These appeared similar in distribution and morphology to the adrenaline cell groups described in the rat. TH-immunoreactive cell groups in the olfactory bulb, hypothalamus, substantia nigra, and ventral tegmental area of the hamster appeared to correspond to the dopaminergic cells groups described in the rat and other species. In addition, as in the rat and cat, numerous TH-positive cells were found in the dorsal motor nucleus of the vagus, the nucleus of the solitary tract, and the area postrema. These observations suggest that catechols may be present in neurons in the cortex, basal forebrain, auditory brainstem, and the parabrachial nucleus of the hamster. These studies also emphasize the need for caution in making generalizations regarding transmitter distributions across species.

Animals↗

PubMed1988

Two populations of somatostatin-immunoreactive neurons in the guinea pig striatum.

Two populations of neurons displaying somatostatin-like immunoreactivity were detected immunohistochemically in the guinea pig striatum using a monoclonal antibody. Sparse, well-stained neurons similar to those described in other species were observed throughout the guinea pig caudate-putamen. These neurons contained both neuropeptide Y and NADPH-diaphorase in addition to somatostatin. A second large population of somatostatin immunoreactive neurons in which these other substances did not coexist was found within the putamen.

Animals↗

PubMed1988

Intra-cerebral cysteamine infusions attenuate the motor response to dopaminergic agonists.

Previous studies have suggested that somatostatin neurons in the basal ganglia may be involved in motor activity. In the present experiments, the effects of cysteamine, a drug which reduces somatostatin levels, on the basal and dopamine-mediated motor activities were examined in the rat. Neither intra-striatal nor intra-accumbens infusions of cysteamine had any effect on motor activity prior to the administration of dopamine agonists. However, intra-striatal cysteamine infusions reduced the duration of the stereotypic behavior induced by systemic apomorphine. In addition, intra-accumbens infusions of cysteamine produced a slight reduction in the locomotor response induced by amphetamine. The direct intra-cerebral infusion of cysteamine produced a significant depletion in the levels of somatostatin at the site of injections as measured by radioimmunoassay. These results indicate that somatostatin neurons in the basal ganglia may modulate the motor responses following dopaminergic activation, and further support the presence of a dopamine-somatostatin interaction in this region.

Animals↗

PubMed1988

Retrograde transport of [3H]-GABA by lateral olivocochlear neurons in the rat.

Injection of [3H]-gamma aminobutyric acid (GABA) into the perilymphatic space of the rat's inner ear resulted in retrograde labeling of a portion of the small efferent olivocochlear neurons within the lateral superior olivary nucleus (LSO). These cells were of similar size as LSO neurons stained immunohistochemically with antibodies to the GABA synthesizing enzyme glutamic acid decarboxylase (GAD). They were of fusiform shape, but smaller than principal LSO cells, which did not stain for GAD and did not accumulate [3H]-GABA. Other efferent cochlear and vestibular neurons were not labeled.

Animals↗

PubMed1988

Legionella cincinnatiensis sp. nov. isolated from a patient with pneumonia.

A Legionella-like organism (strain 72-OH-H [= ATCC 43753]) was isolated from an open-lung biopsy specimen from a hemodialysis patient with end-stage renal disease and bronchopneumonia. Growth characteristics and gas-liquid chromatographic profiles of the isolate were consistent with those for Legionella spp. The isolate was presumptively identified as a Legionella longbeachae serogroup 1 strain by direct immunofluorescence staining. However, the organism was serologically distinct in the slide agglutination test with absorbed antisera. DNA hybridization studies showed that strain 72-OH-H constitutes a new Legionella species, which is named Legionella cincinnatiensis (ATCC 43753).

Adult↗

PubMed1988

Effects of systemic and intracerebroventricular cysteamine on dexamethasone-induced suppression of corticosterone levels in the rat.

To investigate whether somatostatin systems plays a significant role in the regulation of the hypothalamic-pituitary-adrenal axis, the effects of cysteamine, a drug which reduces somatostatin levels, on the dexamethasone-induced suppression of plasma corticosterone levels were examined in the rat. Male Long Evans rats were handled daily for 1 week prior to receiving a standard dexamethasone suppression test. On the 1st day, rats received a 9.00 a.m. saline injection and blood samples were taken from the tail at 1.00 p.m. On the 2nd day, rats received dexamethasone or saline at 9.00 a.m. and a second blood sample was taken at 1.00 p.m. Experimental groups were pretreated with systemic injections of cysteamine, 5 min or 14 h, prior to receiving dexamethasone. Additional groups, previously implanted with guide cannulae, were given an infusion of cysteamine or saline into the lateral ventricle 14 h prior to dexamethasone. Circulating corticosterone levels were determined by radioimmunoassay. Rats were sacrificed immediately following each experiment and the hypothalamus dissected and assayed for levels of somatostatin immunoreactivity. The results of the first experiment showed that dexamethasone (10 micrograms/kg) alone reduced plasma corticosterone levels from control values (174 +/- 36 ng/ml) to undetectable levels (less than 25 ng/ml). Pretreatment with cysteamine 5 min prior to dexamethasone, while having no significant effect on basal corticosterone levels, completely blocked the dexamethasone-induced suppression of corticosterone levels. Similar observations were obtained with rats pretreated with cysteamine 14 h prior to dexamethasone. In contrast, intracerebroventricular cysteamine pretreatment did not block the dexamethasone-induced suppression of corticosterone levels. These results add further evidence in support of an involvement of somatostatin systems in the regulation of the hypothalamic-pituitary-adrenal axis.

Animals↗

PubMed1988

The ultrastructure of somatostatin-immunoreactive cell bodies, nerve fibers and terminals in the dorsal horn of rat spinal cord.

The distribution and ultrastructure of somatostatin-immunoreactive neurons, nerve fibers and axon terminals in the dorsal horn of rat thoracic spinal cord were studied by immunohistochemistry at both the light and electron microscopic levels. Somatostatin-immuno reactive neurons were predominantly observed in Rexed laminae I and II of the dorsal horn of spinal cord. Somatostatin-immunoreactive electron dense peroxidase material was concentrated in the Golgi apparatus and rough endoplasmic reticulum of the somatostatin-immunoreactive neurons, and was characteristically sparse in other regions of the cytoplasm. In the somatostatin-immunoreactive fibers and terminals, immunoreactive electron dense material was concentrated in the microtubules and large synaptic vesicles.

Animals↗