Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in peptide YY receptor binding were investigated at various intervals after limbic seizures induced in rats by an intraperitoneal injection of kainic acid (10-12 mg/kg). Six to 24 h after kainic acid, specific peptide YY binding, representing Y1 and Y2 neuropeptide Y receptor subtypes, was markedly enhanced in the strata radiatum and oriens CA3 (increase by up to 185% and 178% of control values, respectively). Seven and 30 days after kainic acid, a reduction by up to 63% was found. The basal and kainic acid-induced changes in peptide YY binding were mainly represented by Y2 receptor sites. In the hilus of the dentate gyrus, an increase of global peptide YY binding by up to 400% was observed after 24 h which became attenuated to 125% after 30 days. In the molecular layer of the dentate gyrus global peptide YY binding increased by up to 87% between six and 24 h after kainic acid injection and was reduced by 37% after 30 days. Similar changes were observed in the cerebral cortex. Whereas in the hilus of the dentate gyrus peptide YY binding consisted mainly of Y2 sites, it represented predominantly Y1 receptors in the molecular layer and the cortex. The decline in global and Y2 specific peptide YY binding observed at 30 days in the hippocampus proper was prevented in animals protected from seizure-induced brain damage by an anticonvulsant dose of phenobarbital 3 h after injection of kainic acid. In the stratum moleculare of the dentate gyrus, Y2 specific binding was significantly enhanced while global peptide YY binding was slightly decreased compared to controls. These results show lasting changes in neuropeptide Y receptor binding sites after the acute seizures induced by kainic acid. Since neuropeptide Y modulates glutamatergic neurotransmission, these modifications may play an important role in the hippocampal excitability of chronically epileptic rats.
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PMID:Autoradiographic analysis of neuropeptide Y receptor binding sites in the rat hippocampus after kainic acid-induced limbic seizures. 884 35

To clarify the cellular localization of neuropeptide-Y receptor subtypes in the dentate gyrus and CA3 sector of the rat dorsal hippocampus and their changes after kainic acid-induced seizures, we used receptor autoradiography to measure [125I]PYY binding to Y1 and Y2 receptors after colchicine treatment. Fifteen days after colchicine infusion in the dorsal hippocampus granule cells and their mossy fibres degenerated while the hilar interneurons and CA3 pyramidal cells were spared. This treatment markedly decreased [125I]PYY binding to Y1 receptors in the molecular layer of the dentate gyrus (-82%) and in the hilus (-70%). [125I]PYY binding to Y2 receptors was reduced by 40% and 48%, respectively, in the CA3 region and in the hilus. Thirty days after kainic acid treatment, [125I]PYY binding to Y1 receptors was decreased by 35% in the molecular layer of the dentate gyrus whereas the binding to Y2 receptors was increased by 116% in the hilus. The effect of colchicine in kainic acid-treated rats indicates that these plastic changes occur selectively on granule cell projections.
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PMID:Cellular localization of neuropeptide-Y receptors in the rat hippocampus: long-term effects of limbic seizures. 885 1

Kainic acid-induced limbic seizures cause lasting increases in neuropeptide Y (NPY) expression in hippocampal granule cells/mossy fibers. The expression of NPY-Y1 receptors in these neurons were investigated, using in situ hybridization for Y1 mRNA and receptor autoradiography with the Y1-specific ligand [125I][Pro34]PYY. Six hours after kainic acid-induced seizures, Y1 receptor mRNA levels decreased by 80% in granule cells and concomitantly increased (by 75%) in CA2 pyramidal neurons. Subsequently, persistent decreases in Y1 mRNA were seen, both in the stratum granulosum and in CA2. Changes in mRNA concentrations were accompanied by a transient, although non-significant, increase in [125I][Pro34]PYY binding in the molecular layer of the dentate gyrus after 4-6 h which was succeeded by a lasting decrease in binding which indicates a persistent down-regulation of Y1 receptors in hippocampal areas in kainic acid-induced epilepsy.
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PMID:Altered expression of NPY-Y1 receptors in kainic acid induced epilepsy in rats. 925 81

Electrical kindling of the rat dorsal hippocampus induced significant changes in the binding of 125I-peptide YY to Y1 and Y2 subtypes of neuropeptide Y receptors and in their mRNA levels in the area dentata as assessed by quantitative receptor autoradiography and in situ hybridization histochemistry. Binding to Y1 receptor sites decreased by 50% (p < 0.05) in the molecular layer of the stimulated dentate gyrus, 2 days after preconvulsive stage 2 and 1 week or 1 month after generalized stage 5 seizures compared with sham-stimulated rats. Binding to Y2 receptor sites increased bilaterally by 36-87% (p < 0.05) in the hilus at stage 2 and 1 week or 1 month after stage 5. No significant changes were observed after one afterdischarge or in the other hippocampal subfields or in the cortex. Y1 receptor mRNA signal decreased bilaterally by 50-64% (p < 0.01) in the granule cell layer, 6 h but not 24 h after stages 2 and 5. The Y2 receptor mRNA signal was enhanced by 283% (p < 0.01) in the stimulated granule cell layer 24 h after stage 2. At 6 and 24 h after stage 5, mRNA levels were increased both ipsilaterally (283 and 360%, respectively; p < 0.01) and contralaterally (190 and 260%, respectively; p < 0.05). No significant changes in level of either mRNA was found following one afterdischarge. These modifications, and the enhanced neuropeptide Y release previously shown in the hippocampus, suggest that kindling is associated with lasting changes in neuropeptide Y-mediated neurotransmission.
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PMID:Distinct changes in peptide YY binding to, and mRNA levels of, Y1 and Y2 receptors in the rat hippocampus associated with kindling epileptogenesis. 952 78

Neuropeptide Y-Y2 receptor mRNA and binding were investigated after local injection of excitatory amino acid receptor agonists into the rat hippocampus. The general metabotropic glutamate receptor (mGluR) agonist (1S,3R)ACPD (200 and 400 nmol) and the group I mGluR agonist DHPG (50 nmol) enhanced Y2 receptor mRNA levels in granule cells (by up to 470%) and [125I]PYY(3-36) binding in mossy fibers. The group I mGluR antagonist 4-CPG (200 nmol) inhibited the action of (1S,3R)ACPD. On the other hand, AMPA and NMDA enhanced Y2 receptor expression only at neurodegenerative doses (> 0.3 and 3 nmol, respectively). It is suggested that seizure-induced Y2 receptor expression in granule cells may be mediated by group I mGluRs.
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PMID:Metabotropic glutamate receptors mediate activation of NPY-Y2 receptor expression in the rat dentate gyrus. 969 26

125I-[Leu31,Pro34]peptide YY (PYY) and 125I-PYY3-36, initially described as selective neuropeptide Y Y1 and Y2 receptor ligands, respectively, were recently shown to label also Y4 and Y5 receptors. We used receptor autoradiography to assess whether these ligands can be reliably used to investigate the various neuropeptide Y receptors in rat forebrain. In most of the brain regions examined (in coronal sections at the level of dorsal hippocampus), specific 125I-[Leu31,Pro34]PYY binding was completely inhibited by 1 microM BIBP-3226, a selective Y1 receptor ligand, but unaffected by 10 nM rat pancreatic polypeptide, selectively inhibiting Y4 receptors, suggesting that Y4 receptors are present in negligible numbers compared with Y1 receptors in the areas examined. Significant numbers of BIBP-3226-insensitive 125I-[Leu31,Pro34]PYY binding sites were measured in the CA3 subfield of the hippocampus only, possibly representing Y5 receptors. 125I-PYY3-36 binding was unchanged by 1 microM BIBP-3226, whereas a population of 125I-PYY3-36 binding sites was sensitive to 100 nM [Leu31,Pro34]neuropeptide Y, likely representing Y5 receptors. The possibility of distinguishing between Y2 and Y5 receptors using 125I-PYY3-36 as radioligand was validated by their different regional distribution and their distinct changes 24 h after kainate seizures, i.e., binding to Y5 receptors was selectively decreased in the outer cortex, whereas binding to Y2 receptors was enhanced in the hippocampus. Thus, the use of selective unlabeled compounds is required for distinguishing the various receptor subtypes labeled by 125I-[Leu31,Pro34]PYY and 125I-PYY3-36 in rat brain tissue.
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PMID:Autoradiographic reevaluation of the binding properties of 125I-[Leu31,Pro34]peptide YY and 125I-peptide YY3-36 to neuropeptide Y receptor subtypes in rat forebrain. 1009 75

Repeated electroconvulsive stimulations and other seizure modalities produce an increase in neuropeptide Y synthesis and local release in the rat hippocampus, and perhaps as a consequence, a change in the concentration of neuropeptide Y binding sites in the same region. The aim of the present study was to determine possible changes in the expression of neuropeptide Y receptor subtypes affected by repeated stimulations in the hippocampus. Rats were exposed to 14 daily stimulations, and the brains were removed 24h after the last stimulation. For in vitro receptor autoradiography and in situ hybridisation histochemistry, the brains were frozen, sectioned, and levels of neuropeptide Y binding sites and messenger RNA expressions were determined quantitatively on sections from the same animals. In order to determine the contribution of different neuropeptide Y receptor subtypes, serial sections were incubated with either 125I-labelled peptide YY alone or the same radio-labelled peptide mixed with an excess of a number of displacing compounds with affinity for either neuropeptide Y receptor subtype Y1, Y2, or both. Binding studies revealed that the majority of peptide YY binding sites was represented by Y2, and that electroconvulsive stimulations reduced the binding capacity or the concentration of this receptor. A prominent reduction of Y1-preferring binding sites was determined in the dentate gyrus, and to a lesser extent in the CA1 and CA3 regions. Similarly, the treatment produced a significant reduction of Y2-preferring binding sites in the CA1 and CA3 region, but not in the granular cell layer of the dentate gyrus. Using semi-quantitative in situ hybridization, Y1 receptor messenger RNA level in the granular cell layer of the dentate increased by the stimulations. In the same region, Y2 receptor messenger RNA was expressed in low to undetectable amounts, but after the repeated stimulations, this transcript was found in moderate to high levels. These data suggest that the neuropeptide Yergic system in the dentate gyrus and the pyramidal cell layer are affected by the treatment, and that this includes both Y1 and Y2 receptor subtypes. Because levels of messenger RNA and binding are distinctly regulated, the turnover of both Y1 and Y2 molecules is strongly increased under electroconvulsive stimulations, suggesting that the intrahippocampal neuropeptide Yergic neurotransmission is also increased under the stimulations.
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PMID:Electroconvulsive stimuli enhance both neuropeptide Y receptor Y1 and Y2 messenger RNA expression and levels of binding in the rat hippocampus. 1085 9

It has been suggested that the anticonvulsant effects of neuropeptide Y (NPY) could be mediated by the activation of Y(2) and/or Y(5) receptors. NPY Y(1) receptor levels are known to decrease and Y(2) to increase in rat models of epilepsy. By using an autoradiographic approach, we investigated whether epilepsy models (kainic acid and kindling) are also associated with changes in Y(5) receptors. Compared with naive controls, [125I][Leu(31), Pro(34)]PYY/BIBP3226-insensitive (Y(5)) binding sites in the hippocampus (strata oriens and radiatum of CA3 and CA1) and in the neocortex (superficial layers) were unchanged in sham-stimulated rats, but reduced by approximately 50% in kindled rats (seven days after the last stimulus evokes seizure), and further reduced (to approximately -90%) 1h after a kindled seizure. Additionally, Y(5) receptor binding sites in the hippocampus and in the neocortex were unchanged 6h after kainic acid injection, but were highly reduced at 12 and 24h. No changes in Y(5) binding levels were found in the dentate gyrus and the pyramidal cell layer of the hippocampus. The present data suggest that changes in Y(5) receptor levels occur in epilepsy models. These changes may play a role in seizure expression and/or in the maintenance of kindling hyperexcitability.
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PMID:Decreased levels of neuropeptide Y(5) receptor binding sites in two experimental models of epilepsy. 1089 13

The anti-convulsive effects of neuropeptide Y have been suggested in several animal models of epilepsy. We have found the sustained increase of neuropeptide Y contents and the seizure-induced elevation of hippocampal messenger RNA in a novel spontaneous epileptic mutant rat: Noda epileptic rat. In the present study, we investigated the change of neuropeptide Y Y1 and Y2 receptor messenger RNA expressions and binding sites in the hippocampus following a spontaneous generalized tonic-clonic seizure of Noda epileptic rat. Furthermore, the binding sites of a more recently isolated receptor subtype, neuropeptide Y Y5 receptors, were also evaluated by receptor autoradiography. A marked elevation of neuropeptide Y immunoreactivity in the mossy fiber, and Y2-receptor up-regulation in the dentate gyrus were observed in the hippocampus of Noda epileptic rat, which coincided with the previous results of the other epileptic models. In contrast, Y1-receptor down-regulation was not found after a spontaneous seizure of Noda epileptic rat while this occurs in kindling and after kainic acid-induced seizures. [125I][Leu31, Pro34]peptide YY/BIBP 3226-insensitive (Y5 receptor) binding sites in CA1 stratum radiatum were significantly decreased following a spontaneous seizure of Noda epileptic rat. The present results suggest that a spontaneous seizure of Noda epileptic rat induces significant changes in neuropeptide Y-mediated transmission in the hippocampus via Y2 and Y5 receptors, but not Y1 receptors. Therefore, specific subset of neuropeptide Y receptor subtypes might be involved in the epileptogenesis of Noda epileptic rat.
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PMID:Differential changes in messenger RNA expressions and binding sites of neuropeptide Y Y1, Y2 and Y5 receptors in the hippocampus of an epileptic mutant rat: Noda epileptic rat. 1245 77

Neuropeptide Y (NPY) in the central nervous system is a major regulator of food consumption and energy homeostasis. It also regulates blood pressure, induces anxiolysis, enhances memory retention, affects circadian rhythms and modulates hormone release. Five Y receptors (Y1, Y2, Y4, Y5 and Y6) are known to mediate the action of NPY and its two other family members, peptide YY (PYY) and pancreatic polypeptide (PP). Increased NPY signaling due to elevated NPY expression in the hypothalamus leads to the development of obesity and its related phenotypes, Type II diabetes and cardiovascular disease. Dysregulation in NPY signaling also causes alterations in bone formation, alcohol consumption and seizure susceptibility. The large number of Y receptors has made it difficult to delineate their individual contributions to these physiological processes. However, recent studies analysing NPY and Y receptor overexpressing and knockout models have started to unravel some of the different functions of these Y receptors. Particularly, the use of conditional knockout models has made it possible to pinpoint a specific function to an individual Y receptor in a particular location.
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PMID:NPY and Y receptors: lessons from transgenic and knockout models. 1533 71


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