Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cells displaying highly condensed pyknotic nuclei, the most characteristic feature of apoptosis, are considered as dead cells in neural tissue. The present study aimed to devise methods that could allow the neurogenetic and phenotypic characterization of dying pyknotic cells. In the first set of experiments, pregnant mice were labeled at embryonic days E10-E16 with pulses of 5'-bromodeoxyuridine visualization of BrdU after an immunoperoxidase reaction. In addition to normal, healthy immunopositive nuclei, these preparations displayed a number of pyknotic nuclei that were immunoreactive for BrdU. Both the regional and the temporal distribution of BrdU-positive pyknotic cells were coincidental with the peaks of dead cells in neural tissue. For example, pulses of BrdU at E10-E11 resulted in the visualization of immunoreactive pyknotic cells in the subplate and white matter of the cerebral cortex in early postnatal (P) animals. Thus, the times of generation (birthdates) of cells subjected to degenerative processes can be unequivocally identified. In the second set of experiments, brain sections from unlabeled littermates were immunostained for a variety of neural and glial markers and counterstained with bisbenzimide, to find antigens which, by being present in degenerate pyknotic cells, could indicate the phenotype of such cells. Although no pyknotic cells were positively immunostained for neurofilaments, neuropeptide Y, somatostatin, vasoactive intestinal polypeptide, or vimentin, a number of pyknotic cells were found to be immunoreactive for microtubule-associated protein 2, gamma-aminobutyric acid, calbindin 28KD, and glial fibrillary acidic protein. The percentage of pyknotic cells labeled with neural antigens accounted for more than 20% of the total number of pyknotic cells in a given brain region. In contrast, GFAP-positive pyknotic cells represented up to 50% of the total pyknotic cell population. The method shown here has enabled us to determine that both neurons and glial cells undergo degeneration during normal development.
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PMID:Characterization of the phenotype and birthdates of pyknotic dead cells in the nervous system by a combination of DNA staining and immunohistochemistry for 5'-bromodeoxyuridine and neural antigens. 831 74

Although the entorhinal cortex is a key structure connecting the hippocampal formation with the rest of the cerebral cortex, little is known about its early chemoanatomical development in primates. In the present study, a cytoarchitectonic analysis and immunocytochemical detection of somatostatin, neurotensin, parvalbumin, calbindin-D 28K, DARPP-32, as well as tyrosine hydroxylase, dopamine-beta-hydroxylase, and serotonin, were carried out on serial sections of the entorhinal cortex of six rhesus monkey fetuses aged E47 to E90 (gestation period 165 days). At E56 the cortical plate of the entorhinal cortex already exhibited a sublamination; at E64 the lamina dissecans was partly formed, allowing the emergence of the lamina principalis externa and interna, and at E83 most of the regional and laminar subdivisions characteristic of the adult cortex could be identified, except for the rhinal sulcus restricted to a small dimple. The neurochemical development paralleled the early cytoarchitectonic differentiation, both largely preceding that of the neighboring cortical areas. The somatostatin-like immunoreactive innervation, first detected at E56, was very dense as early as E64 and displayed by E83 a laminar distribution similar to that found in the adult. Labeled neurons indicated an intrinsic origin for this innervation but an extrinsic connection might be present as labeled fibers in the subplate of the entorhinal cortex were in continuity with positive fibers in the intermediate zone of the hippocampal formation. A faint neurotensin-like immunoreactivity first detected at E64 became prominent at E83 in the entorhinal cortex but stopped abruptly at the anlage of the rhinal sulcus. The lack of neurotensin-labeled neurons contrasted with their presence in other parts of the hippocampal region and suggested a precocious extrinsic connection. Only rare parvalbumin-LIR neurons were detected at midgestation, whereas calbindin-D 28K was expressed from E47 on in Cajal-Retzius cells and from E56 on in various types of neurons in the cortical plate and subplate. Most characteristic was a category of medium-sized, deeply stained calbindin-LIR neurons, present only in the lamina principalis externa and possibly corresponding to the population of large neurons described by Kostovic et al. (1990, Soc Neurosci Abstr 16:846) in early developing entorhinal cortex of human fetuses. These and probably other neurons were also DARPP-32-positive, suggesting the possibility of an early dopaminergic regulation. Indeed, the monoaminergic innervation of the entorhinal cortex was detected from E56 on and gradually increased in density, displaying areal and laminar differences in the distribution of the dopaminergic, noradrenergic, and serotoninergic afferents.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neurochemical development of the hippocampal region in the fetal rhesus monkey. I. Early appearance of peptides, calcium-binding proteins, DARPP-32, and monoamine innervation in the entorhinal cortex during the first half of gestation (E47 to E90). 835 10

Neuroanatomical methods were used to determine if cocaine irreversibly injures neurons. Despite acute and chronic high-dose treatments for months that produced stereotyped behavior and seizures, and the use of a sensitive silver impregnation method, we were unable to find any evidence of neuronal damage anywhere in the brain. Since expression of the inducible 72 kDa heat shock protein (HSP72) is a sensitive indicator of potentially toxic neuronal stress, we next determined if cocaine evoked HSP72 expression. Even high doses of cocaine that evoked seizures did not induce HSP72 immunoreactivity anywhere within the brain, whereas kainic acid produced widespread HSP72 immunoreactivity and irreversible injury. Having failed to find indications of frank neurotoxicity, we examined peptide and protein cell marker immunoreactivities in search of cocaine-induced changes. Although cocaine treatment had no obvious effects on the patterns of hippocampal calbindin-D28K, somatostatin-, tyrosine hydroxylase- and parvalbumin immunoreactivities, cocaine reliably altered neuropeptide Y-like immunoreactivity (NPY-LI). Most notably, NPY-LI was expressed in hippocampal dentate granule cells and pyriform cortical neurons, which do not normally express it. Conversely, we noted decreased NPY-LI in dentate hilar neurons that normally do express it. Since both changes in NPY-LI were seen only in cocaine-treated rats that exhibited seizures, the role of seizure activity per se in producing the NPY changes was addressed in normal rats by electrical stimulation of the perforant path. Like cocaine, perforant path stimulation for as little as 15min evoked NPY-LI in granule cells but did not replicate the cocaine-induced decrease in hilar cell NPY-LI. These results suggest that cocaine does not irreversibly injure neurons in the rat, even at doses that induce seizures. However, cocaine produces long-lasting changes in NPY expression that are of unknown functional significance. Our inability to demonstrate cocaine-induced neuronal damage in rats should in no way be taken as evidence of its safety in humans.
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PMID:Cocaine neurotoxicity and altered neuropeptide Y immunoreactivity in the rat hippocampus; a silver degeneration and immunocytochemical study. 835 18

Excitotoxin lesions induced by quinolinic acid (QA) were made unilaterally in the caudate nucleus and putamen of 12 rhesus monkeys. Both acute (2-3 weeks) and chronic (4-6 months) effects were evaluated. Excitotoxin striatal lesions were characterized by a central zone of intense astrogliosis and marked neuronal depletion, which was surrounded by a transition zone in which there was partial neuronal sparing throughout the entire lesioned side. Immunocytochemical and enzyme histochemical markers for both large and medium-sized aspiny- and spiny-striatal neurons clearly demonstrated a selective pattern of neuronal vulnerability to the excitotoxic effects of QA within lesioned striata. Medium-sized spiny neurons containing calbindin Dk28, enkephalin, and substance P were disproportionately lost, while aspiny neuronal subpopulations containing NADPH diaphorase (NADPH-d) and choline acetyltransferase activity (ChAT) were relatively spared. Combined labeling by NADPH-d enzyme histochemistry and Nissl staining, as well as NADPH-d histochemistry and calbindin Dk28 immunocytochemistry, demonstrated significant increases in the ratio of aspiny to spiny neurons within the lesioned striata. Neurochemical measurements confirmed a loss of GABA and substance P-like immunoreactivity yet no significant depletion of somatostatin-like immunoreactivity, neuropeptide Y-like immunoreactivity, or ChAT were seen. The striatal patch-matrix pattern persisted, as demonstrated by acetylcholinesterase activity. The pattern was altered, however, in the chronic animals, such that the matrix zone was significantly reduced, while the total area of patches remained within normal limits. Ultrastructural analysis confirmed axon sparing lesions with neuronal loss and astrogliosis. Pretreatment of 3 monkeys with MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, blocked striatal QA neurotoxicity. The present results provide an experimental primate model which closely resembles the neuropathologic and neurochemical features of Huntington's disease. These findings further strengthen the possibility that an NMDA receptor-mediated excitotoxic process plays a role in the pathogenesis of this disorder.
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PMID:Excitotoxin lesions in primates as a model for Huntington's disease: histopathologic and neurochemical characterization. 843 51

In order to learn about the factors regulating the postnatal development of neocortical peptidergic neuron populations, we have analysed neurons expressing neuropeptide Y (NPY) by immunohistochemistry and in situ hybridization in developing and adult rat visual cortical areas 17 and 18a in vivo, and in organotypic slice cultures of rat visual cortex. For quantitative analysis, the percentage of NPY mRNA-expressing neurons was determined in supragranular layers I-IV, in infragranular layers V and VI and in the white matter. In vivo, this percentage increased in visual areas 17 and 18a until postnatal day 21 in supra- and infragranular layers. Initially, in both areas the neurons were about equally distributed in supra- and infragranular layers (a ratio of 1:1). During the second postnatal month, the percentage of NPY mRNA-expressing neurons in area 18a declined by approximately 50% in both supra- and infragranular layers, so that the ratio of 1:1 remained constant. In contrast, in area 17 the percentage of neurons in supragranular layers remained fairly constant, but it declined to 50% in infragranular layers, so that by postnatal day 70 the ratio was gradually shifted to 2:1. Throughout development, area 18a contained significantly more NPY mRNA-expressing neurons than area 17. In organotypic slice cultures, a high density of NPY mRNA-expressing neurons had appeared by 10 days in vitro. A much higher percentage of neurons expressed NPY mRNA. The ratio of labelled neurons in supra- versus infragranular layers was 1:1. Both ratio and percentage remained constant from 10-85 days in vitro. The decline in vivo was not caused by an elimination of transient cell types. All cell types persisted into adulthood. Four NPY peptide-immunoreactive neuronal types were classified by axonal morphology in organotypic slice cultures and in vivo; they include (i) cells in layer VI/white matter with horizontal axons and ascending collaterals, (ii) cells in layers V/VI with descending axon and horizontal collaterals, (iii) Martinotti cells in layers V/VI with ascending axons, and (iv) cells in layers III-V with columnar axons. Two further types, bipolar cells with axons descending from dendrites and small basket cells with short horizontal axons, both found in vivo in layers II/III, could not be unequivocally identified in organotypic slice cultures. The NPY-immunoreactive neuron types had already formed a dense innervation of the cultures by 10 days in vitro, which remained stable for up to 85 days in vitro, and resembled the innervation observed in vivo. NPY peptide-immunoreactive neurons in organotypic slice cultures and in vivo were distributed in cortical layers II/III, V and VI and the white matter, but rarely in layers I and IV, which corresponded to the distribution of NPY mRNA-expressing neurons. However, with in situ hybridization more neurons were detectable, especially in layers II/III. A majority of NPY mRNA-expressing neurons co-localized NPY peptide, somatostatin and calbindin. We conclude that intrinsic cues were sufficient to drive the molecular expression of the NPY phenotype, the morphological differentiation and the stabilization of an organotypic NPY innervation in organotypic slice cultures. However, the area- and lamina-specific changes observed in vivo were not observed under monoculture conditions.
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PMID:Areal differences of NPY mRNA-expressing neurons are established in the late postnatal rat visual cortex in vivo, but not in organotypic cultures. 854 71

The synaptic input of interneurons with horizontal dendrites in stratum oriens of the CA1 region was investigated, with particular attention to the portion of synapses originating from local pyramidal cells. Most of these GABAergic interneurons are known to contain somatostatin, and terminate on pyramidal dendrites in conjunction with entorhinal afferents in stratum lacunosum-moleculare. A smaller number of horizontal cells in this layer are immunoreactive for calbindin, and project to the medial septum. Selective ischaemic degeneration was used to label local axon collaterals of CA1 pyramidal cells, and immunostaining for mGluR1 or calbindin to visualise somatostatin- and calbindin-containing horizontal interneurons, respectively, at the stratum oriens-alveus border. The number of degenerating and intact synaptic boutons was counted on mGluR1- as well as on calbindin-positive dendrites and somata, whereas in another group of animals the proportion of GABA-immunoreactive synapses was estimated on calbindin-positive dendrites. On average, > 60% of the total presynaptic elements of both cell types were degenerating, i.e. originated from CA1 pyramidal cells, whereas GABA-positive boutons, which are known to survive ischaemia, are likely to account for a large proportion of non-degenerating boutons. Thus the vast majority of presumed excitatory synapses on somatostatin- and calbindin-containing horizontal neurons derives from local collaterals of CA1 pyramidal cells. The remaining GABA-negative synapses surviving ischaemia may also originate from CA1 pyramidal cells, e.g. from those in the ventral hippocampus, which are rarely damaged by global forebrain ischaemia. Alternative sources may include subcortical afferents known to innervate interneurons, or ipsi- and contralateral CA3 pyramidal cells, which, according to the present results, may account only for a negligible number of synapses on these interneurons types. We conclude that somatostatin-containing neurons at the oriens-alveus border of CA1, which are likely to mediate an inhibitory control of the efficacy and/or plasticity of entorhinal synapses on pyramidal cell dendrites, are driven primarily in a feed-back manner. The source of afferent excitation for calbindin-containing horizontal neurons in this region is very similar, suggesting that the GABAergic hippocamposeptal feed-back is also activated by local pyramidal cell collaterals.
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PMID:Synaptic input of horizontal interneurons in stratum oriens of the hippocampal CA1 subfield: structural basis of feed-back activation. 854 73

The cellular nature of the giant eosinophilic cells of tuber and of the cells comprising subependymal giant cell astrocytoma (SEGA) in tuberous sclerosis (TS) remains unclear. To assess the characteristics of these lesions, 13 tubers and 6 SEGA were immunohistochemically studied with glial and neuron-associated antigens. In addition to conventional ultrastructure, 6 tubers and 8 SEGA were subjected to immunoelectron microscopic study for glial fibrillary acidic protein (GFAP) and somatostatin. Eosinophilic giant cells of tubers were positive for vimentin (100%), GFAP (77%) and S-100 protein (92%); such cells were also found to a various extent to be reactive for neuron-associated antigens, including neurofilament (NF) proteins (38%) or class III beta-tubulin (77%). SEGA also showed variable immunoreactivity for GFAP (50%) or for S-100 protein (100%); NF epitopes, class III beta-tubulin, and calbindin 28-kD were expressed in 2 (33%), 5 (83%) and 4 (67%) cases, respectively. Cytoplasmic staining for somatostatin (50%), met-enkephalin (50%), 5-hydroxytryptamine (33%), beta-endorphin (33%) and neuropeptide Y (17%) was noted in SEGA, but not in tubers. Ultrastructurally, the giant cells of tubers and the cells of SEGA contained numerous intermediate filaments, frequent lysosomes and occasional rectangular or rhomboid membrane-bound crystalloids exhibiting lamellar periodicity and structural transition to lysosomes. Some SEGA cells showed features suggestive of neuronal differentiation, including stacks of rough endoplasmic reticulum, occasional microtubules and a few dense-core granules. Furthermore, in one case of tuber, a process of a single large cell was seen to be engaged in synapse formation. Intermediate filaments within a few cells of both lesions were decorated by gold particle-labeled GFAP antiserum. Within the tumor cells of SEGA, irregular, non-membrane-bound, electron-lucent areas often contained somatostatin-immunoreactive particles, whereas the latter could not be detected in tuber. The present study provides further evidence of divergent glioneuronal differentiation, both in the giant cells of tubers and the cells of SEGA. The findings of similar cells at different sites, including the subependymal zone, white matter ("heterotopias"), and cortex indirectly supports the idea that these lesions of TS result from a migration abnormality.
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PMID:Tuber and subependymal giant cell astrocytoma associated with tuberous sclerosis: an immunohistochemical, ultrastructural, and immunoelectron and microscopic study. 854 29

The striatal distribution of the substance P receptor (SPR) protein was examined in relation to its ligand, the neuro-peptide SP, as well as to the neurochemical and compartmental composition of the neostriatum in rhesus monkeys (Macaca mulatta) in immunohistochemical experiments. About 2% of striatal neurons, displaying varicose, virtually spine-free dendrites characteristic of large and medium-sized aspiny interneurons, expressed SPR immunoreactivity. SPR/choline acetyltransferase, SPR/somatostatin, SPR/GABA, SPR/calbindin D28k, and SPR/parvalbumin double immunolabeling experiments demonstrated that SPR-positive cells are either cholinergic or somatostatinergic. Comparison of SP and SPR immunoreactivities in double-labeled and adjacent single-labeled sections revealed compartment-specific match and mismatch between the densities of the peptide and receptor. A matching high density of SP fibers and SPR cells and dendrites was only observed in the rim of the striosome compartments. To our knowledge, this is the first evidence for an anatomical border comprised of dendritic processes that separate striatal compartments. We have termed these zones "striocapsules," because they encircle and encapsulate striosomal cell islands. In the striatal matrix, an abundance of SPR-labeled profiles was complemented with light SP staining. By contrast, in the core of the striosomes, SPR labeling was sparse and SP staining intense. SP-positive axon-like puncta frequently contacted SPR-positive dendrites in all striatal compartments. The SP receptor/ligand match indicates a sharp increase in the efficacy of SP action in the striocapsules, and suggests that the influence of SP might be heightened in this striatal subcompartment.
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PMID:Distribution and neurochemical character of substance P receptor (SPR)-immunoreactive striatal neurons of the macaque monkey: accumulation of SP fibers and SPR neurons and dendrites in "striocapsules" encircling striosomes. 872 8

The chemical codings of neurons that project from the small intestine, caecum, proximal colon, distal colon and rectum to the coeliac ganglion of the guinea pig were investigated. The coeliac ganglion was injected with the retrogradely transported dye Fast Blue, and each of the regions was examined 6 days later in wholemounts that had been prepared for immunohistochemical localisation of pairs of antigens. In both the small and large intestines, all intestinofugal neurons were immunoreactive (IR) for choline acetyltransferase (ChAT). In each region of the large intestine, the largest population, representing 50-60% of retrogradely labelled neurons in each region, was immunoreactive for ChAT, bombesin (BN), calbindin (Calb) and nitric oxide synthase (NOS). Most intestinofugal neurons in the small intestine contain bombesin and VIP-IR along with ChAT-IR but none contain either Calb or NOS. Thus, nerve endings of enteric origin in the coeliac ganglion that contain NOS-IR or Calb-IR come from the large intestine and those with bombesin-IR but not NOS-IR are from the small intestine. The gastric wall was injected with Fast Blue in order to label noradrenergic (NA) neurons in the coeliac ganglion and to determine, by localisation of NOS and bombesin-IR, whether they receive inputs from the small and large intestine. Some NA neurons received inputs from the large intestine (and perhaps also from the small intestine) and some received inputs exclusively from the small intestine. Most NA neurons that received intestinofugal inputs had the chemical code NA/-; some were immunoreactive for somatostatin (NA/SOM neurons), but those with IR for neuropeptide Y (NA/NPY) rarely received intestinofugal inputs.
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PMID:Chemical coding of neurons that project from different regions of intestine to the coeliac ganglion of the guinea pig. 878 75

Physiological and morphological characteristics of GABAergic nonpyramidal cells in frontal cortex of young rats identified immunohistochemically as containing somatostatin or vasoactive intestinal polypeptide (VIP) were studied in vitro by whole-cell recording and biocytin injection. We have found that most somatostatin- or VIP-containing neurons were different from two other types of GABAergic cells, the parvalbumin-containing fast-spiking cells and the late-spiking cells (neurogliaform cells). In response to injected currents, somatostatin- or VIP-containing nonpyramidal cells showed either bursts of a few spikes on a slow-depolarizing hump, burst-spiking nonpyramidal cells, or single spikes only on depolarization, regular-spiking nonpyramidal cells. Morphologically, both somatostatin- and VIP-containing cells had vertical axonal arbors terminating in symmetrical synapses that were immunoreactive for GABA in electron micrographs. Somatostatin cells included neurons with main ascending axons sending collaterals into layer I (Martinotti cells in deep layers). Some of the Martinotti cells in layer V also contained calbindin D 28k. VIP cells included neurons the main descending axons of which had more descending than ascending collaterals (bipolar cells and double bouquet cells). Two other morphological forms of the VIP cells were those with short descending axons with collaterals bearing multiple boutons on other cell bodies (small basket cells) or with short ascending main axons with collaterals forming arcades (arcade cells). Some of these neurons also contained calretinin. From these results, it appears that the GABAergic neurons controlling circuits in the neocortical layers may be characterized further based on whether they contain somatostatin or VIP.
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PMID:Physiological and morphological identification of somatostatin- or vasoactive intestinal polypeptide-containing cells among GABAergic cell subtypes in rat frontal cortex. 878 46


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