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)

Fully hippocampus-kindled rats were examined 1 day and 1 month after the last stimulation for changes in somatostatin (SS)-, neuropeptide Y (NPY)-, and calbindin (CaBP)-immunoreactivity (ir) and SS- and NPY-mRNA in situ hybridization (ISH). One day after the last stimulation, there was marked, bilateral increase in SS- and NPY-ir in the outer part of the dentate molecular layer. The cell bodies of dentate hilar SS- and NPY-containing neurons, known to project to this area, also appeared to display increased immunoreactivity as well as an increased ISH signal for SS and NPY mRNA. Bilateral de novo expression of NPY-ir in dentate mossy fiber projection to dentate hilus and CA3 was also evident, but we noted no corresponding NPY-mRNA signal in the parent cell bodies, the dentate granule cells. After 1 month, the levels of NPY-ir and ISH signal appeared essentially normal. In contrast, the levels of SS apparently were decreased, although not yet normal. CaBP-ir was markedly and selectively reduced in dentate granule cell bodies, dendrites, and mossy fibers 1 day after the last stimulation, but after 1 month CaBP-ir appeared essentially normal. Because kindling, once established, is a permanent phenomenon, the observed transient changes in SS, NPY, and CaBP in specific hippocampal terminal fields and neuronal populations cannot be associated specifically with kindling. Rather, they relate to the repeated high-frequency stimulations and may serve as protective measures against deleterious effects of such stimulations.
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PMID:Kindling induces transient changes in neuronal expression of somatostatin, neuropeptide Y, and calbindin in adult rat hippocampus and fascia dentata. 798 24

According to electrophysiological studies, the subcortically denervated hippocampus has been suggested as a model for limbic epilepsy. We investigated a) whether fimbrial lesioning leads to any biochemical or morphological changes in the rat hippocampus, b) if these changes give any explanation to the previously indicated hyperexcitability, and c) if the changes are in line with the findings in other experimental models and human epilepsy. The fimbria-fornix transection was done by aspiration. Four months later, spontaneous EEG activities were recorded, and the hippocampal formation was processed for histology. In addition, a separate group of lesioned rats was used for hippocampal amino acid analysis. Hyperexcitable functioning of the hippocampus was seen as frequent and rhythmic spiking activity in 25% of the fimbria-fornix-lesioned rats, although the rest of them had spikes occasionally. The amino acids analysis revealed a notable decrease in the concentration of GABA but no significant changes in the amount of excitatory amino acids. This suggests impaired GABAergic functioning but does not exclude possible abnormalities in the release of both excitatory and inhibitory amino acids. The number of somatostatin-immunoreactive (SOM-IR) neurons, a subpopulation of GABAergic neurons, was decreased in all the areas of the hippocampus (CA3 > CA1 > hilus), but this was statistically significant only in the CA3 area. Interestingly, it is the region from which interictal spiking activity in the subcortically denervated rat presumable originates. Immunostaining for synaptophysin showed a dense band of granules in the inner molecular layer of the dentate gyrus, indicating probable synaptic reorganization of associational afferents.
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PMID:Biochemical and morphological changes in the rat hippocampus following transection of the fimbria-fornix. 809 58

The physiological characteristics and significance of long-term potentiation in the hippocampus were summarized. In particular, it was pointed out that different mechanisms are involved in the production of hippocampal LTP between the mossy fiber-CA3 system and other systems such as Schaffer collateral-CA1, fimbrial fiber-CA3 and commissural/associational fiber-CA3. Furthermore, the epsilon-subspecies of protein kinase C (PKC) was demonstrated to be exclusively located at the presynaptic terminals in the hippocampus and activated by arachidonic acid, and this enzyme is suggested to be involved in the production of LTP through a phosphorylation of GAP-43, while the gamma-subspecies of PKC may be postsynaptically involved in LTP through an activation of NMDAR1. The production of LTP in the hippocampus is facilitated by many factors such as epidermal growth factor, fibroblast growth factors, somatostatin, M1 receptor agonists and many drugs like anirasetam, bifemelane, idebenone, indeloxazine and vinpocetine, but inhibited by M2-receptor agonists, scopolamine and midazolam. In addition to electrophysiological methods, LTP-like phenomena in 2-deoxyglucose uptake and leucine incorporation can be detected. These LTP phenomena in several animal models will be useful as indices for evaluating facilitatory actions of various compounds on learning/memory functions.
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PMID:[Pharmacology of long-term potentiation]. 810 51

The expression of muscarinic acetylcholine receptors (mAChRs) in glutamic acid decarboxylase (GAD)-positive cells in the different strata of CA1, CA3, and the dentate gyrus (DG) of the dorsal hippocampus is examined by way of quantitative immunofluorescent double labeling employing M35, the monoclonal antibody raised against purified mAChR protein. Of all GAD-positive neurons, 97.5% express mAChRs. Conversely, 92.9% of the muscarinic cholinoceptive nonpyramidal neurons express GAD. These results indicate that the vast majority of the gamma-aminobutyric acid (GABA)ergic neurons express mAChRs. In addition to GAD, parvalbumin (PARV) and somatostatin (SOM) are two neurochemical substances notably expressed in GABAergic neurons. In order to examine whether the entire muscarinic cholinoceptive nonpyramidal cell group can be characterized by these three GABAergic markers, a cocktail of GAD, PARV, and SOM was used in a fluorescent double-labeling experiment with M35. These results show that 97.2% of all muscarinic cholinoceptive nonpyramidal neurons can be neurochemically characterized by the content of GAD, PARV, and SOM. In conclusion, nearly all GABAergic cells express mAChRs and, conversely, virtually the entire muscarinic cholinoceptive nonpyramidal cell group belongs to the GABAergic cell population. This study, therefore, provides anatomical evidence for an extensive neuronal connectivity of the hippocampal muscarinic cholinoceptive nonpyramidal system and the inhibitory GABAergic circuitry.
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PMID:GABAergic neurons of the rat dorsal hippocampus express muscarinic acetylcholine receptors. 822 Nov 58

Intracerebral or intraperitoneal injections of kainic acid, an agonist at a class of glutamate receptors, have been extensively used to model temporal lobe epilepsy. In the present study we compared the types and distributions of selectively vulnerable neurons in the ipsi- and contralateral hippocampi following unilateral kainate injections into the CA3 subfield in order to examine whether "proximal" or "distant" neuronal damage resembled the pathology, and possibly also the mechanism, of human temporal lobe epilepsy. The degeneration of principal cells in the different hippocampal subfields was visualized by silver impregnation, and the loss of various types of non-principal cells was studied by immunostaining for the calcium binding proteins parvalbumin, calbindin-D28k and calretinin, as well as for somatostatin. In the first series of experiments various concentrations (ranging from 0.1 to 1 mg/ml) and volumes (0.5-2 microliters) of kainate were tested to induce reproducible damage in the contralateral hippocampus. The optimal dose, employed in the subsequent vulnerability studies, was found to be 3 x 0.5-microliter injections (over a period of 10 min) of a concentration of 0.33 mg/ml under ether anaesthesia, which was discontinued immediately after injection. Anaesthesia with equithesin was found to prevent contralateral cell death. Most if not all pyramidal cells in the CA3 region degenerated on the ipsilateral side, whereas the dentate granule cells, and the majority of CA1 pyramidal cells were resistant. A strikingly different pattern was found on the contralateral side, where CA1 pyramidal cells were almost completely lost, but the CA3 region (with the exception of CA3c) and the dentate gyrus remained intact. Three subpopulations of non-principal cells were found to be vulnerable in both hemispheres, the hilar somatostatin cells, spiny calretinin cells and mossy cells, as well as the spiny calretinin cells in stratum lucidum of CA3. The other subpopulations were resistant, except for those within the effective injection site. We propose that the "distant" (contralateral) damage resembles the pattern, and probably also the mechanism, of cell death in human temporal lobe epilepsy, whereas the ipsilateral damage does not.
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PMID:Selective neuronal death in the contralateral hippocampus following unilateral kainate injections into the CA3 subfield. 824 63

The mechanism of delayed death of pyramidal cells in the hippocampal CA1 region and the acute death of various types of hilar neurons after ischemia is still unknown. Excitotoxicity may play a role in ischemic cell death, a prerequisite of which is the development of increased excitability or an enhanced excitatory transmission in the selectively vulnerable subfields of the hippocampus. Such changes may take place upon the loss or malfunction of local inhibitory neurons in the early postischemic period. In the present study we examined the vulnerability of non-pyramidal neurons containing a recently discovered calcium binding protein, calretinin, in the rat hippocampus following 15 min ischemia induced by four-vessel occlusion. Immunostaining for calretinin enabled us to visualize a new type of spiny non-pyramidal cell in the hippocampus specifically associated with the mossy fiber system. This cell type is present exclusively in regions where mossy fiber terminals occur, i.e. in the hilus of the dentate gyrus and in stratum lucidum of the CA3 subfield. A selective loss of immunoreactivity in these neurons was already observed at 12-24 h after ischemia, when the pyramidal cells in the CA1 region showed no signs of damage. At a survival time of two to three days, most if not all spiny calretinin-immunoreactive cells had disappeared from the hippocampus. Other types of calretinin-containing GABAergic neurons were also reduced in number, but only at a time when CA1 pyramidal cells also started to degenerate, i.e. two to three days after ischemia. We speculate that the early loss of spiny calretinin-containing cells, together with other non-pyramidal cells associated with the mossy fiber system (somatostatin-containing neurons and mossy cells of the hilus), may result in pathological network activity in the hippocampus, which may ultimately lead to an increased excitatory transmission and delayed pyramidal cell death in the CA1 region.
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PMID:Early degeneration of calretinin-containing neurons in the rat hippocampus after ischemia. 825 22

Much of the work on forebrain ischemia in the hippocampus has focused on the phenomenon of delayed neuronal death in CA1. It is established that dentate granule cells and CA3 pyramidal cells are resistant to ischemia. However, much less is known about interneuronal involvement in CA3 or ischemic injury in the dentate hilus other than the fact that somatostatin neurons in the latter lose their immunoreactivity. We combined two sensitive methods--heat-shock protein (HSP72) immunocytochemistry and a newly developed Gallyas silver stain for demonstrating impaired cytoskeletal elements--to investigate the extent of ischemic damage to CA3 and the dentate hilus using the four-vessel-occlusion model for inducing forebrain ischemia. HSP72-like immunoreactivity was induced in neuronal populations previously shown to be vulnerable to ischemia. In addition, a distinct subset of interneurons in CA3 was also extremely sensitive to ischemia, even more so than the CA1 pyramidal cells. These neurons are located in the stratum lucidum of CA3 and possess a very high density of dendritic spines. In silver preparations, they were among the first to be impregnated as "dark" neurons, before CA1 pyramidal cells; microglial reaction was also initiated first in the stratum lucidum of CA3. Whereas CA1 damage was most prominent in the septal half of the hippocampus, hilar and CA3 interneuronal damage had a more extensive dorsoventral distribution. Our results also show a far greater extent of damage in hilar neurons than previously reported. At least four hilar cell types were consistently compromised: mossy cells, spiny fusiform cells, sparsely spiny fusiform cells, and long-spined multipolar cells. A common denominator of the injured neurons in CA3 and the hilus was the presence of spines on their dendrites, which in large part accounted for the far greater number of mossy fiber terminals they receive than their non-spiny neighbors. We suggest that the differential vulnerability of neuronal subtypes in these two regions may be attributed to their extremely dense innervation by the mossy fibers and/or the presence of non-NMDA receptor subtypes that are highly permeable to calcium. In addition, early impairment of these spiny CA3 cells and hilar neurons after ischemia may be causal to delayed neuronal death in the CA1 pyramidal cells.
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PMID:Vulnerability of mossy fiber targets in the rat hippocampus to forebrain ischemia. 836 55

The nicotinic cholinergic antagonist alpha-bungarotoxin (alpha-BT) binds throughout the rat hippocampal formation. The binding is displaceable by d-tubocurarine. The most heavily labeled cells are GABA-containing interneurons in the dentate and in Ammon's horn. These neurons have several different morphologies and contain several neuropeptides. alpha-BT-labeled interneurons in the dentate are small cells between the granular and molecular layers that often contain neuropeptide Y. alpha-BT-labeled interneurons in CA1 are medium-sized interneurons, occasionally found in stratum pyramidale, but more often found in stratum radiatum and stratum lacunosum moleculare. These neurons often contain cholecystokinin. The largest alpha-BT-labeled interneurons are found in CA3, in both stratum radiatum and stratum lucidum. These neurons are multipolar and frequently are autofluorescent. They often contain somatostatin or cholecystokinin. These large interneurons have been found to receive medial septal innervation and may also have projections that provide inhibitory feedback directly to the medial septal nucleus. The cholinergic innervation of the hippocampus from the medial septal nucleus is under the trophic regulation of NGF and brain-derived neurotrophic factor, even in adult life. Expression of mRNA for both these factors is increased in CA3 and the dentate after intraventricular administration of alpha-BT, but not after administration of the muscarinic antagonist atropine. alpha-BT-sensitive cholinergic receptors on inhibitory interneurons may be critical to medial septal regulation of the hippocampal activity, including the habituation of response to sensory input.
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PMID:Alpha-bungarotoxin binding to hippocampal interneurons: immunocytochemical characterization and effects on growth factor expression. 847 87

The distribution of somatostatin receptors (SRIF-R) was analyzed in the limbic system of the adult rat by in vitro autoradiography with [125I-Tyr0,DTrp 8]S14 as a radioligand. Precise quantification of the density of binding sites, at 0.2 mm intervals throughout the different areas revealed a marked heterogeneity of labeling in most structures. In particular, SRIF-R were concentrated in the basal (104.4 +/- 3.3 fmol/mg proteins) and basolateral amygdaloid nuclei (94.8 +/- 4.3 fmol/mg proteins), and in the nucleus of the lateral olfactory tract (121.6 +/- 2.4 fmol/mg proteins), whereas moderate densities were detected in the amygdalo-hippocampal nucleus (76.4 +/- 2.8 fmol/mg proteins). The medial (41.3 +/- 1.9 fmol/mg proteins) and the central (24.0 +/- 1.4 fmol/mg proteins) amygdaloid nuclei contained lower SRIF-R concentrations. It appears from these observations, in the light of the anatomical pathways of the amygdala, that intra-amygdalian SRIF-containing neurons project to the amygdalo-hippocampal nucleus, and that SRIF-R in the basolateral complex are the target of afferents from limbic cortical areas. SRIF-R were detected at different levels of the hippocampal formation but their distribution was more restricted than that of SRIF-containing fibers. The maximal density of sites was detected in the ventral and dorsal parts of the subiculum (115.0 +/- 3.4 and 87.0 +/- 2.8 fmol/mg proteins, respectively) and in the parasubiculum (100.1 +/- 5.4 fmol/mg proteins). In Ammon's horn, the stratum oriens and stratum radiatum of the CA1 field were the only sites enriched in SRIF-R (74.1 +/- 2.0 and 74.6 +/- 1.9 fmol/mg proteins, respectively). The apparent lack of receptors in the pyramidal cell layer indicated that, in Ammon's horn, SRIF is involved in intra-hippocampal communication. Low levels of receptors were found in the hippocampal CA2 and CA3 fields. SRIF-R in the dentate gyrus were mainly concentrated in the molecular layer (57.3 +/- 1.2 fmol/mg proteins). A very high density of sites was also observed in the entorhinal cortex (up to 123.1 +/- 1.5 fmol/mg proteins). A clear mismatch between SRIF and SRIF-R was detected in the septum and the habenula. In the profound layers of the cingulum and retrosplenial cortex, a heterogeneous distribution of SRIF-R was observed. High concentrations of sites were detected in the rostral zone of the cingulate cortex (93.4 +/- 2.0 fmol/mg proteins) while the posterior cingulate only exhibited moderate concentrations of sites (66.5 +/- 0.7 fmol/mg proteins).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Quantitative autoradiography of somatostatin receptors in the rat limbic system. 851 16

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


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