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

In the present study we examined the laminar distributions of four types of chemically defined subpopulations of non-principal neurons, that is, those immunoreactive for parvalbumin (PV), calretinin (CR), nitric oxide synthase (NOS) and somatostatin (SS), in the rat hippocampus, by estimating their approximate numerical densities (NDs) and percentages in specific layers according to the 'disector' principle. CR-immunoreactive (CR-IR) neurons and NOS-IR neurons were scattered throughout layers, but among layers in each subdivision their NDs were largest in the principal cell layers, where 30-45% of CR-IR and NOS-IR somata in each subdivision were located. In addition, CR-IR and NOS-IR somata were also concentrated at the border between the stratum radiatum (SR) and stratum lacunosum moleculare (SLM) in the CA1 region, where the NDs of these neurons were far larger than those in the SR/SLM as a whole and close to those in the stratum pyramidale (SP) (CR-IR somata at the ventral level and NOS-IR somata at the dorsal level) or larger (NOS-IR neurons at the ventral level). The NDs of CR-IR somata were dorsoventrally different in all layers of the CA3 region, the SR/SLM in the CA1 region and the hilus and the granule cell layer (GCL) of the dentate gyrus (DG), whereas the NDs of NOS-IR somata were dorsoventrally different in all layers of the CA3 region and the SP in the CA1 region. In contrast, approx. 90% of somatostatin-like immunoreactive (SS-LIR) neurons were located in the stratum oriens/alveus (SO/SA) in the CA1 region and in the hilus of the DG, where they were the most predominant cell type among the four types of non-principal cells. In contrast, in the CA3 region, SS-LIR somata were scattered in various layers. The majority (50-70%) of PV-IR neurons were located in the principal cell layers, whereas one-fourth to one-third of them were located in the SO/SA and hilus. The NDs in the SP of the CA1 and CA3 regions showed a significant dorsoventral difference. Although PV-IR somata were most numerous among the four non-principal cell groups in the SP of the dorsal CA1 region, they were not necessarily predominant in the principal layers in other regions, that is, in the ventral CA1 region, CA3 region and DG, where the NDs of CR-IR and/or NOS-IR somata were nearly equal to or larger than that of PV-IR somata. The present study not only reveals the laminar distribution patterns of four types of non-principal neurons in each subdivision quantitatively, but also illustrates the prominent differences in the compositions of four types of non-principal cells in each layer of each subdivision.
 ...
PMID:Laminar distribution of non-principal neurons in the rat hippocampus, with special reference to their compositional difference among layers. 929 10

Metabotropic glutamate receptors (mGluRs) can be divided into three groups based on sequence homology and pharmacology. We studied expression of group I mGluRs (mGluR1 and mGluR5) in identified neurons of the rat neostriatum, neocortex, and hippocampus using in situ hybridization. Tissue sections were hybridized with radiolabeled RNA probes for mGluR1 or mGluR5 and digoxygenin labeled RNA probes detecting somatostatin (SOM), preproenkephalin (ENK), preprotachykinin (SP), glutamic acid decarboxylase 67 (GAD67), parvalbumin (PARV), or choline acetyltransferase (ChAT) mRNA. In the striatum, mGluR1 hybridization signal was observed in all six neuronal populations. The strongest signal was found in SP-positive neurons, with a lower signal in ENK-positive neurons. All striatal interneurons were labeled less intensely than ENK- and SP-positive projection neurons. For striatal mGluR5 mRNA, both SP- and ENK-positive projection neurons were intensely labeled, but only GAD67-positive interneurons exhibited a significant signal. In the neocortex and hippocampus, mGluR1 and mGluR5 hybridization signals were studied in SOM-, GAD67-, and PARV-positive neurons. Hybridization signal for mGluR1 mRNA was intense in SOM-positive neurons of the cortex, CA1, CA3, and dentate gyrus, and weaker in GAD67-positive neurons of CA3 and dentate gyrus. MGluR5 signals were intensely labeled in SOM-, GAD67- and PARV-positive neuronal populations of the cortex and hippocampus. SOM-positive neurons were more intensely labeled in the hippocampus than cortex.
 ...
PMID:Expression of group one metabotropic glutamate receptor subunit mRNAs in neurochemically identified neurons in the rat neostriatum, neocortex, and hippocampus. 933 23

The neuropeptide calcitonin gene-related peptide (CGRP) was localized in the hippocampus and dentate gyrus of the rat by immunocytochemistry at the light and electron microscopic levels. Without colchicine treatment only faint neuropil labelling was found in the inner molecular layer of the dentate gyrus. Following colchicine treatment, a large number of neurons with numerous complex spines along the proximal dendrites were visualized in the hilus of the dentate gyrus, particularly in the ventral areas, and, in addition, staining of the inner molecular layer became stronger. Several CA3c pyramidal cells located adjacent to the hilar region in the ventral hippocampus also appeared to be faintly positive, although in most cases only their axon initial segments were labelled. Outside this region, the subicular end of the CA1 subfield contained occasional CGRP-positive non-pyramidal cells. The hilar CGRP-positive neurons were negative for parvalbumin, calretinin, cholecystokinin and somatostatin, whereas most of them were immunoreactive for GluR2/3 (the AMPA-type glutamate receptor known to be expressed largely by principal cells). Correlated electron microscopy showed that the spines along the proximal dendritic shafts indeed correspond to thorny excrescences engulfed by large complex mossy terminals forming asymmetrical synapses. Pre-embedding immunogold staining demonstrated that CGRP immunoreactivity in the inner molecular layer was confined to axon terminals that form asymmetrical synapses, and the labelling was associated with large dense-core vesicles. The present data provide direct evidence that CGRP is present in mossy cells of the dentate gyrus and to a lesser degree in CA3c pyramidal cells of the ventral hippocampus. These CGRP-containing principal cells terminate largely in the inner molecular layer of the dentate gyrus, and may release the neuropeptide in conjunction with their 'classical' neurotransmitter, glutamate.
 ...
PMID:Mossy cells of the rat dentate gyrus are immunoreactive for calcitonin gene-related peptide (CGRP). 938 4

In rat CA1 hippocampal pyramidal neurons (HPNs), somatostatin (SST) has inhibitory postsynaptic actions, including hyperpolarization of the membrane at rest and augmentation of the K+ M-current. However, the effects of SST on synaptic transmission in this brain region have not been well-characterized. Therefore we used intracellular voltage-clamp recordings in rat hippocampal slices to assess the effects of SST on pharmacologically isolated synaptic currents in HPNs. SST depressed both (R, S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate and N-methyl--aspartate (NMDA) receptor-mediated excitatory postsynaptic currents (EPSCs) in a reversible manner, with an apparent IC50 of 22 nM and a maximal effect at 100 nM. In contrast, SST at concentrations up to 5 microM had no direct effects on either gamma-aminobutyric acid-A (GABAA) or GABAB receptor-mediated inhibitory postsynaptic currents (IPSCs). The depression of EPSCs by SST was especially robust during hyperexcited states when polysynaptic EPSCs were present, suggesting that this peptide could play a compensatory role during seizurelike activity. SST effects were greatly attenuated by the alkylating agent N-ethylmaleimide, thus implicating a transduction mechanism involving the Gi/Go family of G-proteins. Use of 2 M Cs+ in the recording electrode blocked the postsynaptic modulation of K+ currents by SST, but did not alter the effects of SST on EPSCs, indicating that postsynaptic K+ currents are not involved in this action of SST. However, 2 mM external Ba2+ blocked the effect of SST on EPSCs, suggesting that presynaptic K+ channels or other presynaptic mechanisms may be involved. These findings and previous results from our laboratory show that SST has multiple inhibitory effects in hippocampus.
 ...
PMID:Somatostatin depresses excitatory but not inhibitory neurotransmission in rat CA1 hippocampus. 940 20

We re-examined the proposed resistance of the immature brain to seizure-induced damage. In awake, freely moving rat pups, intermittent perforant path stimulation produced selective hippocampal cell loss and reduction in paired-pulse inhibition. During 16 h of stimulation, animals showed frequent wet dog shakes and hind-limb scratching movements but no convulsive motor activity. In situ end-labelling performed 2 h after the end of stimulation showed an intense band of positively-labelled eosinophilic cells with condensed profiles bilaterally in the dentate granule cell layer of stimulated animals. Control animals showed no in situ end-labelling positivity in the dentate gyrus. These cells were not observed 24 h later, suggestive of rapidly scavenged apoptotic cells. One day after the end of stimulation, many necrotic interneurons with eosinophilic cytoplasm and pyknotic nuclei were observed in the hilus of the stimulated dentate gyrus in all rats tested. Hippocampal pyramidal cells in CA1, CA3 and subiculum showed bilateral damage greater on the side of stimulation, and prepiriform cortex sustained bilateral symmetrical lesions. One month after perforant path stimulation, Cresyl Violet staining showed the number of large hilar interneurons (>15 microm) was reduced on the stimulated side (54.1 +/- 12.2) compared to the non-stimulated side (100.5 +/- 10.2 cells, P<0.01). Immunohistochemical analysis showed significant losses in somatostatin (8.5 +/- 1.6 stimulated side, 22.8 +/- 3.8 unstimulated side, P<0.05) and neuropeptide Y (12.8 +/- 3.2 stimulated side, 17.0 +/- 4.1 unstimulated side, P<0.05) immunoreactive cells in the stimulated hilus but no loss of parvalbumin-immunoreactive cells. Significant reductions in paired-pulse inhibition were found after stimulation but there was some return of inhibition by one month. These combined data demonstrate that the immature brain can incur damage as a result of prolonged seizure-like hippocampal activity mimicking status epilepticus in immature rats. The hippocampal damage produced by perforant path stimulation is associated with the immediate loss of physiological inhibition suggesting important modification of excitatory control in an extremely epileptogenic region of the brain.
 ...
PMID:Hippocampal stimulation produces neuronal death in the immature brain. 946 46

In previous studies m2 muscarinic acetylcholine receptor-immunoreactive interneurons and various types of m2-positive axon terminals have been described in the hippocampal formation. The aim of the present study was to identify the types of interneurons expressing m2 receptor and to examine whether the somadendritic and axonal m2 immunostaining labels the same or distinct cell populations. In the CA1 subfield, neurons immunoreactive for m2 have horizontal dendrites, they are located at the stratum oriens/alveus border and have an axon that project to the dendritic region of pyramidal cells. In the CA3 subfield and the hilus, m2-positive neurons are multipolar and are scattered in all layers except stratum lacunosum-moleculare. In stratum pyramidale of the CA1 and CA3 regions, striking axon terminal staining for m2 was observed, surrounding the somata and axon initial segments of pyramidal cells in a basket-like manner. The co-localization of m2 with neurochemical markers and GABA was studied using the "mirror" technique and fluorescent double-immunostaining at the light microscopic level and with double-labelling using colloidal gold-conjugated antisera and immunoperoxidase reaction (diaminobenzidine) at the electron microscopic level. GABA was shown to be present in the somata of most m2-immunoreactive interneurons, as well as in the majority of m2-positive terminals in all layers. The calcium-binding protein parvalbumin was absent from practically all m2-immunoreactive cell bodies and dendrites. In contrast, many of the terminals synapsing on pyramidal cell somata and axon initial segments co-localized parvalbumin and m2, suggesting a differential distribution of m2 receptor immunoreactivity on the axonal and somadendritic membrane of parvalbumin-containing basket and axo-axonic cells. The co-existence of m2 receptors with the calcium-binding protein calbindin and the neuropeptides cholecystokinin and vasoactive intestinal polypeptide was rare throughout the hippocampal formation. Only calretinin and somatostatin showed an appreciable degree of co-localization with m2 (20% and 15%, respectively). Using retrograde tracing, some of the m2-positive cells in stratum oriens were shown to project to the medial septum, accouting for 38% of all projection neurons. The present results demonstrate that there is a differential distribution of m2 receptor immunoreactivity on the axonal vs the somadendritic membranes of distinct interneuron types and suggest that acetylcholine via m2 receptors may reduce GABA release presynaptically from the terminals of perisomatic inhibitory cells, while it may act to increase the activity of another class of interneuron, which innervates the dendritic region of pyramidal cells.
 ...
PMID:Distinct interneuron types express m2 muscarinic receptor immunoreactivity on their dendrites or axon terminals in the hippocampus. 946 48

Somatostatin (SST) is a neuropeptide involved in several central processes. In hippocampus, SST hyperpolarizes CA1 pyramidal neurons and augments the K+ M current (IM). However, the limited involvement of IM at resting potential in these cells suggests that the peptide also may modulate another channel to hyperpolarize hippocampal pyramidal neurons (HPNs). We studied the effect of SST on noninactivating conductances of rat CA1 HPNs in a slice preparation. Using MK886, a specific inhibitor of the enzymatic pathway that leads to the augmentation of IM by SST, we have uncovered and characterized a second conductance activated by the peptide. SST did not affect IM when applied with MK886 or the amplitudes of the slow Ca2+-dependent K+ afterhyperpolarization-current and the cationic Q current but still caused an outward current, indicating that SST acts upon another conductance. In the presence of MK886, SST elicited an outward current that reversed around -100 mV and that displayed a linear current-voltage relationship. Reversal potentials obtained in different external K+ concentrations are consistent with a conductance carried solely by K+ ions. The slope of the current-voltage relationship increased proportionately with the extracellular K+ concentration and remained linear. This suggests that SST opens a voltage-insensitive leak current (IK(L)) in HPNs not an inwardly rectifying K+ current as reported in other neuron types. A low concentration of extracellular Ba2+ (150 M) only slightly decreased the SST-induced effect in a voltage-independent manner, whereas a high concentration of Ba2+ (2 mM) completely blocked it. Extracellular Cs+ (2 mM) did not affect the outward SST current but inhibited the inward component. We conclude that SST inhibits HPNs by activating two different K+ conductances: the voltage-insensitive IK(L) and the voltage-dependent IM. The hyperpolarizing effect of SST at resting membrane potential appears to be mainly carried by IK(L), whereas IM dominates at slightly depolarized potentials.
 ...
PMID:Somatostatin increases a voltage-insensitive K+ conductance in rat CA1 hippocampal neurons. 949 4

Neurocalcin (NC) is a recently described calcium-binding protein isolated and characterized from bovine brain. NC belongs to the neural calcium-sensor proteins defined by the photoreceptor cell-specific protein recoverin that have been proposed to be involved in the regulation of calcium-dependent phosphorylation in signal transduction pathways. We analyzed the distribution and morphology of the NC-immunoreactive (IR) neurons in the rat dorsal hippocampus and the coexistence of NC with GABA and different neurochemical markers which label perisomatic inhibitory cells [parvalbumin (PV) and cholecystokinin (CCK)], mid-proximal dendritic inhibitory cells [calbindin D28k (CB)], distal dendritic inhibitory cells [somatostatin (SOM) and neuropeptide Y (NPY)], and interneurons specialized to innervate other interneurons [calretinin (CR) and vasoactive intestinal polypeptide (VIP)]. NC-IR cells were present in all layers of the dentate gyrus and hippocampal fields. In the dentate gyrus, NC-IR cells were concentrated in the granule cell layer, especially in the hilar border, whereas in the CA fields they were most frequently found in the stratum radiatum. NC-IR cells were morphologically heterogeneous and exhibited distinctive features of non-principal cells. In the dentate gyrus, pyramidal-like, multipolar and fusiform (horizontal and vertical) cells were found. In the CA3 region most NC-IR cells were multipolar, but vertical and horizontal fusiform cells also appeared. In the CA1 region, where NC-IR cells showed most frequently vertically arranged dendrites, multipolar, bitufted and fusiform (vertical and horizontal) cells could be distinguished. All the NC-IR cells were found to be GABA-IR in all hippocampal layers and regions, and they represented about 19% of the GABA-positive cells. NC/CB, NC/CR and NC/VIP double-labeled cells were found in all hippocampal regions, and represented 29%, 24% and 18% of the NC-IR cells, respectively. NC and CCK did not coexist in the dentate gyrus; however, 9% of the NC-IR cells in the CA fields also contained CCK. No coexistence of NC with PV, SOM or NPY was found in any hippocampal region. We conclude that NC is exclusively expressed by interneurons in the rat hippocampus. NC-IR cells are a morphologically and neurochemically heterogeneous subset of GABAergic non-principal cells, which, on the basis of the known termination pattern of the colocalizing markers, are also functionally heterogeneous and are mainly involved in feed-forward dendritic inhibition in the commissural-associational and Schaffer collateral termination zones (CB containing cells), in innervation of other interneurons (CR- and VIP-containing cells), and in perisomatic inhibition (CCK-containing cells). NC is never present in perisomatic inhibitory PV-containing cells, or in feed-back distal dendritic inhibitory SOM/NPY-containing cells.
 ...
PMID:Neurocalcin-immunoreactive cells in the rat hippocampus are GABAergic interneurons. 958 Mar 16

In situ hybridization and immunocytochemistry were applied to investigate changes in the expression of somatostatin, neuropeptide Y, neurokinin B, cholecystokinin, dynorphin, and Met-enkephalin in the rat hippocampus after administration of a single peroral dose of trimethyltin hydroxide (9 mg/kg). Two time intervals were investigated: 5 days after trimethyltin treatment, when CA3 damage becomes manifest and is associated with increased aggression, seizure susceptibility, and memory deficit, and 16 days after trimethyltin, when neuronal damage is almost maximal and seizure susceptibility is declining. Robust but transient increases of neuropeptide Y, neurokinin B, and Met-enkephalin mRNA levels were revealed in the granule cell layer of the dentate gyrus and increased neuropeptide Y and neurokinin B immunoreactivities were found in mossy fibers. In reverse, dynorphin mRNA and immunoreactivity were decreased transiently in the dentate gyrus and mossy fibers, respectively. Strong over-expression of NPY mRNA was also observed in hilar interneurons and in CA1 and CA3 pyramidal cells as well as in the cortex at 5 days postdosing. Cholecystokinin- or neurokinin B-containing basket cells were preserved, while somatostatin-bearing interneurons were damaged by trimethyltin exposure. These neurochemical changes induced by trimethyltin intoxication strikingly parallel to those observed in animal models of temporal lobe epilepsy and may reflect activation of endogenous protective mechanisms. It is also suggested that hilar interneurons respond differently to trimethyltin exposure, for which neuropeptides are valuable markers.
 ...
PMID:Trimethyltin intoxication induces marked changes in neuropeptide expression in the rat hippocampus. 966 Dec 51

Enkephalins are known to have a profound effect on hippocampal inhibition, but the possible endogenous source of these neuropeptides, and their relationship to inhibitory interneurons is still to be identified. In the present study we analysed the morphological characteristics of met-enkephalin-immunoreactive cells in the CA1 region of the rat and guinea-pig hippocampus, their coexistence with other neuronal markers and their target selectivity at the light and electron microscopic levels. Several interneurons in all subfields of the hippocampus were found to be immunoreactive for met-enkephalin. In the guinea-pig, fibres arising from immunoreactive interneurons were seen to form a plexus in the stratum oriens/alveus border zone, and basket-like arrays of boutons on both enkephalin-immunoreactive and immunonegative cell bodies in all strata. Immunoreactive boutons always established symmetric synaptic contacts on somata and dendritic shafts. Enkephalin-immunoreactive cells co-localized GABA, vasoactive intestinal polypeptide and calretinin. Postembedding immunogold staining for GABA showed that all the analysed enkephalin-immunoreactive boutons contacted GABAergic postsynaptic structures. In double-immunostained sections, enkephalin-positive axons were seen to innervate calbindin D28k-, somatostatin-, calretinin- and vasoactive intestinal polypeptideimmunoreactive cells with multiple contacts. Based on these characteristics, enkephalin-containing cells in the hippocampus are classified as interneurons specialized to innervate other interneurons, and represent a subset of vasoactive intestinal polypeptide- and calretinin-containing cells. The striking match of ligand and receptor distribution in the case of enkephalin-mediated interneuronal communication suggests that this neuropeptide may play an important role in the synchronization and timing of inhibition involved in rhythmic network activities of the hippocampus.
 ...
PMID:Enkephalin-containing interneurons are specialized to innervate other interneurons in the hippocampal CA1 region of the rat and guinea-pig. 975 Nov 50


<< Previous 1 2 3 4 5 6 7 8 9 10