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)

The evolution of cellular damage over time and the selective vulnerability of different neuronal subtypes was characterized in the striatum following 30-minute middle cerebral artery occlusion and reperfusion in the mouse. Using autoradiography we found an increase in the density of [3H]PK11195 binding sites--likely reflecting microglial activation--in the lesion border at 3 days and in the whole striatum from 10 days to 6 weeks. This was accompanied by a distinct loss of [3H]flumazenil and [3H]CGP39653 binding sites from 10 days up to 6 weeks reflecting neuronal loss. Brain ischemia resulted in a substantial loss of medium spiny projection neurons as seen at three days by Nissl staining, TUNEL and immunocytochemistry using antibodies against microtubule-associated protein (MAP2), NeuN, mu-opioid receptors, substance P, L-enkephalin, neurokinin B, choline acetyltransferase, parvalbumin, calretinin and somatostatin. Both patch and matrix compartments were involved in ischemic damage. In contrast, the numbers of cholinergic, GABAergic, and somatostatin-containing interneurons in the ischemic striatum were not different from those in the contralateral hemisphere at 3 and 14 days. A low density of glutamate receptors, the ability to sequester calcium by calcium-binding proteins and other hitherto unidentified factors may explain this relative resistance of interneurons to acute ischemia.
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PMID:Selective neuronal vulnerability following mild focal brain ischemia in the mouse. 1465 51

The mammalian cortical layer I is a convergence site for axons of sub- and intracortical origin, and the apical dendritic tufts of pyramidal neurons. A prominent feature of layer I is an extensive plexus of inhibitory axons, which originate from stellate cells in all cortical laminae. The role of this inhibitory projection in the activity of cortical networks has yet to be determined. We investigated the degree to which inhibitory inputs within layer I affect the activity of the underlying cellular network. Field potentials (FPs) were recorded in layer II/III. Focal application of the GABAA blocker picrotoxin in layer I above the recording pipette or the removal of layer I resulted in larger FP amplitudes for stimulations at control-equal intensities. When inhibition was partially blocked, the removal of layer I caused a significant reduction in the threshold stimulus intensity required for generating epileptiform events, and a rise in the propagation velocity of these events. Immunocytochemistry for chemical markers of interneurons proved that the inhibitory input to layer I is predominantly somatostatin immunoreactive (SM-ir), such that layer I contains approximately one-third of all SM-ir axons in the cortex. Calretinin-immunoreactive axons were also present in layer I at a lower density. We conclude that the impact of layer I on the cortical cellular network includes a significant inhibitory component. This inhibition confers a moderate restraining influence, and its removal increases the excitability of cortical circuits, but not sufficiently to induce epileptic phenomena.
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PMID:Inhibitory effect of mouse neocortex layer I on the underlying cellular network. 1465 24

The endopiriform nucleus, further divided into dorsal and ventral parts, and the neighbouring pre-endopiriform (pEn) nucleus form a region of highly heterogeneous structure involved in numerous physiological and pathological processes. Nonpyramidal neurons of this region containing three neuropeptides-somatostatin (SOM), neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP)-were examined in this study. Their colocalization with three calcium-binding proteins-parvalbumin (PV), calbindin D28k (CB), calretinin (CR), and with nitric oxide synthase (NOS), was investigated by qualitative and quantitative methods. The results are summarized as follows: (1) all studied substances are distributed in neurons of the entire region, (2) SOM-ir neurons constitute the most numerous neuropeptide-containing population, whereas NOS-ir neurons make up the largest population of all studied, (3) colocalizations are found in the endopiriform region (Enr) (SOM with CB, PV and NOS; VIP with CR; NPY with NOS and NOS with CR), (4) heterogeneity of the endopiriform region appears in the differences of cells' shape distributions of single-labeled (SOM-, CR-PV-ir) and double-labeled (SOM/CB-, SOM/PV-, NPY/NOS- and NOS/CR-ir) neurons, as well as in differentiated percentage values of SOM/NOS, NPY/NOS and VIP/CR double-labeled neurons in three studied parts; additionally, differences in distribution of immunoreactive neuropil elements between parts of the region are observed. Numerous regional differences concerning neuronal morphology and immunocytochemical characteristics justify further division of the endopiriform region into distinguished parts. Some immunocytochemical features of the neurons in studied region may contribute to the role in epileptogenesis.
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PMID:Neuropeptide-containing neurons in the endopiriform region of the rat: morphology and colocalization with calcium-binding proteins and nitric oxide synthase. 1467 Jun 36

Mechanical activation of the mucosal lining of the colon by brush stroking elicits an intestinal neural reflex and an increase in short circuit current (Isc) indicative of electrogenic chloride ion transport. We tested whether endogenous nucleotides are physiologic regulators of mucosal reflexes that control ion transport. The brush stroking-evoked Isc response in mucosa and submucosa preparations (M-SMP) of rat colon was reduced by the P2Y1 receptor (R) antagonist 2'deoxy-N6-methyl adenosine 3',5'-diphosphate diammonium salt (MRS 2179) and further blocked by tetrodotoxin (TTX). M-SMP Isc responses to serosal application of the P2Y1 R agonist 2-methylthioadenosine-diphosphate (2MeSADP) or the P2Y2/P2Y4 R agonist 5'uridine-triphosphate (UTP) were reduced but not abolished by TTX. The potency profile of nucleotides for increasing Isc was 5'adenosine-triphosphate (ATP; effective concentration at half maximal response [EC50] 0.65 x 10(4) M) congruent with UTP (EC50 1.0 x 10(-4) M) congruent with 2MeSADP (EC50 = 1.60 x 10(-4) M). Mucosal touch and distention-induced Ca2+ transients in submucous neurons were reduced by apyrase and prevented by blocking the P2Y1 R with MRS 2179 and TTX; denervation of the mucosa. It did not occur by touching a ganglion directly. 2MeSADP Ca2+ responses occurred in subsets of neurons with or without substance P (SP) responses. The potency profile of nucleotides on the neural Ca2+ response was 2MeSADP (5 x 10(-7) M) > UTP (6 x 10(-6) M) > ATP (9 x 10(-5) M). The expression of P2Y R immunoreactivity (ir) in nerve cell bodies was in the order of P2Y1 R > P2Y4 R >> P2Y2 R. P2Y1R ir occurred in the cell somas of more than 90% of neuronal nitric oxide synthase, vasoactive intestinal peptide (VIP), calretinin, or neuropeptide Y (NPY)-ir neurons, 78% of somatostatin neurons, but not in calbindin or SP neurons. P2Y2 R ir was expressed in a minority of SP, VIP, NPY, vesicular acetylcholine transporter, and calcitonin gene-related peptide-ir varicose fibers (5-20%) and those surrounding calbindin (5-20%) neurons. P2Y4 ir occurred mainly in the cell somas of 93% of NPY neurons. Reverse transcriptase polymerase chain reaction of the submucosa demonstrated mRNA for P2Y1R, P2Y2, P2Y4, P2Y6, and P2Y12 Rs. Expression of P2Y1, P2Y2, and P2Y4 protein was confirmed by western blots. In conclusion, endogenous nucleotides acting at P2YRs transduce mechanically evoked reflex chloride ion transport in rat distal colon. Nucleotides evoke reflexes by acting primarily at postsynaptic P2Y1 Rs and P2Y4 R on VIP+/NPY+ secretomotor neurons, at P2Y2 Rs on no more than 2% of VIP+ secretomotor neurons, and 2Y2 Rs mainly of extrinsic varicose fibers surrounding putative intrinsic primary afferent and secretomotor neurons. During mucosal mechanical reflexes, it is postulated that P2Y1 R, P2Y2 R, and P2Y4 R are activated by endogenous ATP, UTP, and 5'uridine-diphosphate.
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PMID:Mechanically evoked reflex electrogenic chloride secretion in rat distal colon is triggered by endogenous nucleotides acting at P2Y1, P2Y2, and P2Y4 receptors. 1468 71

Opioids are thought to control the excitability of hippocampal principal neurons indirectly by inhibiting GABAergic interneurons. However, direct inhibition of hippocampal principal neurons by opioids has also been reported. To understand better the neuromodulatory role of opioids in rat hippocampal circuits, we analyzed types of micro- and delta-opioid receptor (MOR, DOR)-expressing hippocampal neurons. Most MOR-immunoreactive neurons in the granular and pyramidal cell layers exhibited multipolar morphologies characteristic of GABAergic neurons. Virtually all neurons in the hippocampal formation expressing high MOR mRNA levels cocontained the mRNA for glutamic acid decarboxylase (GAD). Most parvalbumin-, several calretinin-, and several pre-proenkephalin-containing neurons expressed the MOR gene in the hippocampal formation. Expression of high DOR mRNA levels was restricted to GAD-positive neurons in the principal cell layers, oriens layer and hilus. More than 90% of the parvalbumin-positive neurons in the hippocampal formation strongly expressed the DOR gene. Granule cells expressing vesicular glutamate transporter 1 (VGLUT1) mRNA contained very low MOR and DOR transcript levels. In VGLUT1-positive pyramidal cells, weak DOR but no MOR gene expression was detected. Whereas most somatostatinergic hilar neurons were negative for MOR and DOR mRNA, somatostatinergic oriens layer neurons frequently expressed these receptors. Taken together, weak expression of MOR and DOR genes in hippocampal principal cells is in concordance with direct opioid-mediated inhibition of principal cells. However, strong expression of the MOR and DOR genes in the hippocampus is restricted to gamma-aminobutyric acid (GABA)ergic neurons, with DORs being selectively expressed in the parvalbumin- and somatostatin-containing subpopulations. Activation of MOR and/or DOR in parvalbumin- and somatostatin-containing neurons, which provide GABAergic inhibition to the perisomatic and distal dendritic regions of principal cells, respectively, is likely to facilitate principal cell excitation.
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PMID:Neuronal types expressing mu- and delta-opioid receptor mRNA in the rat hippocampal formation. 1468 76

Here we have studied the developmental expression of alpha1 subunit of the GABAA receptor in comparison with the expression of alpha2 subunit and several GABAergic markers (parvalbumin (PV), calretinin (CR), somatostatin (SOM), neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP)). The alpha1 expression (mRNA and protein) was low at birth and increased progressively until the adulthood. This expression pattern was similar to that observed for PV, opposite to that of CR (high at birth and decreased continuously until the adulthood) and differed from that observed for the alpha2 and neuropeptides (SOM, NPY and VIP) (in all cases, a clear peak in expression was observed at P10). We further investigated the expression of alpha1, PV and CR by immunohistochemistry. As expected, the alpha1 and the PV expression were low at birth and increased progressively until the adulthood. Both alpha1 and PV were co-expressed by the same interneuronal population, however, the maturation of the alpha1 subunit preceded to that of PV. Finally, we observed a gradient of maturation between the different fields of the hippocampus proper (CA2-3 preceded to CA1 and DG). This gradient could be related to the high expression of CR positive cells and fibers during the first 10 postnatal days, located principally in the stratum lacunosum moleculare of the CA2-3 layers.
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PMID:Postnatal development of the alpha1 containing GABAA receptor subunit in rat hippocampus. 1475 27

Vesicular glutamate transporter type 3 (VGLUT3) containing neuronal elements were characterized using antibodies to VGLUT3 and molecular cell markers. All VGLUT3-positive somata were immunoreactive for CCK, and very rarely, also for calbindin; none was positive for parvalbumin, calretinin, VIP or somatostatin. In the CA1 area, 26.8 +/- 0.7% of CCK-positive interneuron somata were VGLUT3-positive, a nonoverlapping 22.8 +/- 1.9% were calbindin-positive, 10.7 +/- 2.5% VIP-positive and the rest were only CCK-positive. The patterns of coexpression were similar in the CA3 area, the dentate gyrus and the isocortex. Immunoreactivity for VGLUT3 was undetectable in pyramidal and dentate granule cells. Boutons colabelled for VGLUT3, CCK and GAD were most abundant in the cellular layers of the hippocampus and in layers II-III of the isocortex. Large VGLUT3-labelled boutons at the border of strata radiatum and lacunosum-moleculare in the CA1 area were negative for GAD, but were labelled for vesicular monoamine transporter type 2, plasmalemmal serotonin transporter or serotonin. No colocalization was found in terminals between VGLUT3 and parvalbumin, vesicular acetylcholine transporter and group III (mGluR7a,b; mGluR8a,b) metabotropic glutamate receptors. In stratum radiatum and the isocortex, VGLUT3-positive but GAD-negative boutons heavily innervated the soma and proximal dendrites of some VGLUT3- or calbindin-positive interneurons. The results suggest that boutons coexpressing VGLUT3, CCK and GAD originate from CCK-positive basket cells, which are VIP-immunonegative. Other VGLUT3-positive boutons immunopositive for serotonergic markers but negative for GAD probably originate from the median raphe nucleus and innervate select interneurons. The presumed amino acid substrate of VGLUT3 may act on presynaptic kainate or group II metabotropic glutamate receptors.
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PMID:GABAergic basket cells expressing cholecystokinin contain vesicular glutamate transporter type 3 (VGLUT3) in their synaptic terminals in hippocampus and isocortex of the rat. 1498 6

Cerebral cortical functions are conducted by two general classes of neurons: glutamatergic projection neurons and GABAergic interneurons. Distinct interneuron subtypes serve distinct roles in modulating cortical activity and can be differentially affected in cortical diseases, but little is known about the mechanisms for generating their diversity. Recent evidence suggests that many cortical interneurons originate within the subcortical telencephalon and then migrate tangentially into the overlying cortex. To test the hypothesis that distinct interneuron subtypes are derived from distinct telencephalic subdivisions, we have used an in vitro assay to assess the developmental potential of subregions of the telencephalic proliferative zone (PZ) to give rise to neurochemically defined interneuron subgroups. PZ cells from GFP+ donor mouse embryos were transplanted onto neonatal cortical feeder cells and assessed for their ability to generate specific interneuron subtypes. Our results suggest that the parvalbumin- and the somatostatin-expressing interneuron subgroups originate primarily within the medial ganglionic eminence (MGE) of the subcortical telencephalon, whereas the calretinin-expressing interneurons appear to derive mainly from the caudal ganglionic eminence (CGE). These results are supported by findings from primary cultures of cortex from Nkx2.1 mutants, in which normal MGE fails to form but in which the CGE is less affected. In these cultures, parvalbumin- and somatostatin-expressing cells are absent, although calretinin-expressing interneurons are present. Interestingly, calretinin-expressing bipolar interneurons were nearly absent from cortical cultures of Dlx1/2 mutants. By establishing spatial differences in the origins of interneuron subtypes, these studies lay the groundwork for elucidating the molecular bases for their distinct differentiation pathways.
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PMID:Origins of cortical interneuron subtypes. 1502 53

In the hippocampal CA1 region, metabotropic glutamate subtype 1 (mGluR1) receptors have been implicated in a variety of physiological responses to glutamate, which include modulation of synaptic transmission and plasticity, as well as neuronal excitability and synchronization. The mGluR1alpha isoform is characteristically expressed only by nonprincipal cells, and it is particularly enriched in somatostatin (SS)-containing interneurons in stratum oriensalveus. Anatomical and physiological data have indicated the presence of mGluR1alpha in several distinct classes of interneurons with their somata located also in strata pyramidale, radiatum, and lacunosum moleculare. Each different interneuron subtype, as defined by functionally relevant criteria, including input/ output characteristics and expression of selective molecular markers, subserves distinct functions in local hippocampal circuits. We have investigated which of the different CA1 interneuron classes express mGluR1alpha by immunofluorescent labeling, combining antibodies to mGluR1alpha, calcium-binding proteins, and neuropeptides, and by intracellular labeling in vitro. Several types of interneuron that are immunopositive for mGluR1alpha each targeted different domains of pyramidal cells and included (1) O-LM inter-neurons, found to coexpress both SS and parvalbumin (PV); (2) interneurons with target selectivity for other interneurons, expressing vasoactive intestinal polypeptide (VIP) and/or the calcium-binding protein calretinin; (3) procholecystokinin-immunopositive interneurons probably non-basket and dendrite-targeting; and (4) an as-yet unidentified SS-immunoreactive but PV-immunonegative interneuron class, possibly corresponding to oriens-bistratified cells. Estimation of the relative proportion of mGluR1alpha-positive interneurons showed 43%, 46%, and 30% co-labeling with SS, VIP, or PV, respectively. The identification of the specific subclasses of CA1 interneurons expressing mGluR1alpha provides the network basis for assessing the contribution of this receptor to the excitability of the hippocampus.
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PMID:Immunolocalization of metabotropic glutamate receptor 1alpha (mGluR1alpha) in distinct classes of interneuron in the CA1 region of the rat hippocampus. 1509 25

Brain 5-HT2A receptors have been implicated in various behavioural and physiological processes including hippocampus-dependent learning and memory. To clarify the cellular localization and chemical identity of 5-HT2A receptor-immunoreactive (-ir) neurons in the rat septal complex and dorsal hippocampus, an immunofluorescence histochemical study was performed using a monoclonal antibody to the 5-HT2A receptor. Pretreatment with colchicine increased the number of 5-HT2A receptor-ir cell bodies, indicating that the 5-HT2A receptor protein undergoes microtubule-dependent anterograde transport in axons and dendrites. 5-HT2A receptor immunoreactivity was detected in septal cholinergic neurons, identified with an antiserum to the vesicular acetylcholine transporter (VAChT), and in GABAergic cell bodies in the medial septum/diagonal band of Broca, identified with antisera to glutamic acid decarboxylase (GAD) and the calcium-binding protein parvalbumin. In the dorsal hippocampus, 5-HT2A receptor immunoreactivity was demonstrated in cells located in the pyramidal cell layer (CA1-3) throughout the Ammon's horn and in the granular cell layer of the dentate gyrus. Furthermore, 5-HT2A receptor immunoreactivity was present in most hippocampal interneurons identified by the presence of GAD65, parvalbumin, calbindin D-28k, somatostatin and neuropeptide Y. In contrast, 5-HT2A receptor immunoreactivity was present in only a few interneurons containing cholecystokinin and calretinin immunoreactivity. The results suggest that serotonin acting on 5-HT2A receptors can modulate hippocampal functions via direct actions on hippocampal glutamatergic principal cells and indirectly via actions on hippocampal interneurons with different phenotypes as well as GABAergic and cholinergic septohippocampal neurons.
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PMID:Chemical identity of 5-HT2A receptor immunoreactive neurons of the rat septal complex and dorsal hippocampus. 1512 29


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