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

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.
 ...
PMID:Metabotropic glutamate receptors mediate activation of NPY-Y2 receptor expression in the rat dentate gyrus. 969 26

Neuropeptide Y (NPY), a 36 amino acid neuromodulator that is secreted by neurons throughout the peripheral and central nervous system, has been implicated in the control of many physiological processes. We have begun to examine its role in regulation of appetite, behavior, and excitotoxicity by examining mice that are unable to produce NPY as a consequence of gene inactivation. These mutant mice are remarkably normal when reared under standard vivarium conditions. Despite considerable evidence that NPY plays a central role in stimulating appetite, NPY-deficient mice eat normally, grow normally, and refeed after a fast normally. Furthermore, all of their endocrine responses to fasting are normal. The response of NPY-null mice to diet-induced obesity, chemically induced obesity (monosodium glutamate and gold thioglucose), and genetic-based obesity (lethal yellow agouti, Ay; uncoupling protein-diphtheria toxin transgenics, UCP-DT) were all normal. However, NPY deficiency does partially ameliorate the obesity and all of the adverse endocrine effects of leptin deficiency in ob/ob mice. NPY-null mice as well as mice deficient in both NPY and leptin are more sensitive to leptin, suggesting that NPY may normally have a tonic inhibitory action on leptin-mediated satiety signals. NPY-null mice display the normal voracious feeding response to injected NPY. Thus, the only condition where we have observed a role for NPY in body-weight regulation is in the context of complete leptin deficiency--where absence of NPY is beneficial. The activity and general behavior of NPY-null mice are normal. They appear to have normal spatial and contextual learning ability; however, they manifest more anxiety under some conditions. NPY-null mice occasionally display spontaneous, seizure-like events. They also are less able to terminate seizures induced by GABA receptor antagonists or glutamate receptor agonists. These observations are consistent with previous data suggesting that NPY plays an important role in dampening excitotoxicity.
 ...
PMID:Life without neuropeptide Y. 976 8

Neuropeptide Y (NPY) has been shown to depress hyperexcitable activity that has been acutely induced in the normal rat brain. To test the hypothesis that NPY can also reduce excitability in the chronically epileptic human brain, we recorded intracellularly from dentate granule cells in hippocampal slices from patients with hippocampal seizure onset. NPY had a potent and long-lasting inhibitory action on perforant path-evoked excitatory responses. In comparison, the group 3 metabotropic glutamate receptor agonist L-2-amino-4-phosphonobutyric acid (L-AP4) evoked a mild and transient decrease. NPY-containing axons were found throughout the hippocampus, and in many epileptic patients were reorganized, particularly in the dentate molecular layer. NPY may therefore play a beneficial role in reducing granule cell excitability in chronically epileptic human tissue, and subsequently limit seizure severity.
 ...
PMID:NPY inhibits glutamatergic excitation in the epileptic human dentate gyrus. 1040 Sep 74

Kainic acid induces seizures and a rapid induction of immediate early genes and neuronal death. Neuropeptide Y (NPY) is implicated in seizure inhibiting activity. In order to investigate the mechanisms by which NPY inhibits seizure activity, this study was carried out to measure the levels of mRNAs encoding three different immediate early genes, in regions of the hippocampus and relate their induction to the behaviour in the same animals. NPY inhibited both the time spent in seizures, and the number of generalized seizures. However, NPY did not inhibit the induction of c-fos, FosB or junB mRNA in any hippocampal region examined in the same animals, showing lack of correlation between immediate early gene induction and seizure activity.
 ...
PMID:Kainic acid seizure suppression by neuropeptide Y is not correlated to immediate early gene mRNA levels in rats. 1047 Dec 4

Neuropeptide Y (NPY) is an inhibitory neuromodulator expressed abundantly in the central nervous system that is suspected of being an endogenous antiepileptic agent that can control propagation of limbic seizures. Electrophysiological and pharmacological data suggest that these actions of NPY are mediated by G protein-coupled NPY Y2 and NPY Y5 receptors. To determine whether the NPY Y5 receptor (Y5R) is required for normal control of limbic seizures, we examined hippocampal function and responsiveness to kainic acid-induced seizures in Y5R-deficient (Y5R-/-) mice. We report that Y5R-/- mice do not exhibit spontaneous seizure-like activity; however, they are more sensitive to kainic acid-induced seizures. Electrophysiological examination of hippocampal slices from mutant mice revealed normal function, but the antiepileptic effects of exogenously applied NPY were absent. These data demonstrate that Y5R has an important role in mediating NPY's inhibitory actions in the mouse hippocampus and suggest a role for Y5R in the control of limbic seizures.
 ...
PMID:Role of the Y5 neuropeptide Y receptor in limbic seizures. 1055 53

Neuropeptide Y receptors belong to the G-protein-coupled receptor superfamily and mediate a wide variety of physiological functions, including blood pressure regulation, hormone release, appetite control, seizure propensity, cognition, and emotion. The recent description of a new neuropeptide Y receptor, Y5, expressed in hypothalamic nuclei in rat brain, raised the possibility that Y5 was the receptor mediating the feeding and appetite-related functions of neuropeptide Y. This was supported by subsequent data showing a downregulation of this "feeding" receptor in the brain of the obese Zucker rat (Widdowson, 1997). We have performed a detailed analysis of Y5 expression in rat brain using in situ hybridization histochemistry with digoxygenin-labeled riboprobes and compared this to expression of Y5 in human brain regions. mRNA for the human Y5 receptor was highly expressed in human hypothalamic and thalamic nuclei. In particular, the arcuate and paraventricular nuclei of the hypothalamus, midline thalamic nuclei, and amygdala showed very high levels of expression with high levels in hippocampus. The striking conservation of expression of the rat and human Y5 receptors in relevant hypothalamic and other nuclei implies sharing of a major neuroendocrine functional role by this receptor.
 ...
PMID:Conservation of expression of neuropeptide Y5 receptor between human and rat hypothalamus and limbic regions suggests an integral role in central neuroendocrine control. 1057 27

Neuropeptide Y (NPY) is widely distributed throughout the central nervous system (CNS) and is one of the most conserved peptides in evolution, suggesting an important role in the regulation of basic physiological functions, including learning and memory. In addition, experimental studies have suggested that NPY, together with its receptors, may have a direct implication in several pathological disorders, including epilepsy/seizure. NPY-like immunoreactivity and NPY receptors have been shown to be present throughout the brain, but is concentrated in the hippocampus. The hippocampal formation has been repeatedly implicated in the modulation of cognition, as well as the pathogenesis of seizure. This review will concentrate on the hippocampal distribution of NPY, its receptors and the putative role played by this peptide in seizure, together with the regulation of cognitive function associated with learning and memory.
 ...
PMID:Multiple receptors for neuropeptide Y in the hippocampus: putative roles in seizures and cognition. 1061 7

Repetitive transcranial magnetic stimulation (rTMS) is increasingly used as a therapeutic tool in various neurological and psychiatric disorders, and we recently found that it has a neuroprotective effect both in vitro and in vivo. However, the neurochemical mechanisms underlying the therapeutic effects are still unknown. We investigated the effects of long-term rTMS on the expression of brain-derived neurotrophic factor (BDNF), cholecystokinin (CCK), and neuropeptide tyrosine (NPY) mRNA in rat brain. In situ hybridization revealed a significant increase in BDNF mRNA in the hippocampal areas CA3 and CA3c, the granule cell layer, as well as in the parietal and the piriform cortex after rTMS. BDNF-like immunoreactivity was markedly increased in the same areas. A significant increase in CCK mRNA was observed in all brain regions examined. NPY mRNA expression, in contrast, was not altered. The present results suggest that BDNF may contribute to the neuroprotective effects of rTMS. Furthermore, the rTMS-induced changes in BDNF and CCK expression are similar to those reported after antidepressant drug treatment and electroconvulsive seizures, suggesting that a common molecular mechanism may underlie different antidepressant treatment strategies.
 ...
PMID:Long-term repetitive transcranial magnetic stimulation increases the expression of brain-derived neurotrophic factor and cholecystokinin mRNA, but not neuropeptide tyrosine mRNA in specific areas of rat brain. 1088 47

Megencephaly, enlarged brain, is a major sign in several human neurological diseases. The mouse model for megencephaly (mceph/mceph) has an enlarged brain, presumably due to brain cell hypertrophy, and exhibits neurological and motor disturbances with seizure-like activity, as well as disturbances in the insulin-like growth factor system. Here, we report that expression of the neuropeptides cholecystokinin, enkephalin, galanin and neuropeptide Y is dramatically changed in mceph/mceph brains compared to wild type, as revealed by in situ hybridization and immunohistochemistry. The changes were confined to discrete brain regions and occurred in a parallel fashion for peptides and their transcripts. For cholecystokinin, mceph/mceph brains had region-specific up- and down-regulations in several layers of the hippocampal formation and increased levels in, especially ventral, cortical regions. Enkephalin messenger RNA expression was up-regulated in the dentate gyrus granular layer and in ventral cortices, but down-regulated in the CA1 pyramidal layer. Enkephalin-like immunoreactivity was elevated in mossy fibers of the hippocampus and the ventral cortices. Galanin expression was increased in several layers and interneurons of the hippocampal formation, as well as in ventral cortices. Galanin-like immunoreactivity was reduced in nerve terminals in the forebrain. Neuropeptide Y expression was increased in the hippocampal formation and ventral cortices. Whether the mainly increased peptide levels contribute to the excessive growth of the brain or represent a consequence of this growth and/or of the neurological and motor disturbances remains to be elucidated.
 ...
PMID:Expression of cholecystokinin, enkephalin, galanin and neuropeptide Y is markedly changed in the brain of the megencephaly mouse. 1100 68

Neuropeptide Y (NPY) is a potent modulator of excitatory synaptic transmission and limbic seizures. NPY is abundantly expressed in the dentate gyrus and is thought to modulate hippocampal excitability via activation of presynaptic Y2 receptors (Y2R). Here we demonstrate that NPY, and commonly used Y2R-preferring (NPY(13-36)) and Y5 receptor (Y5R)-preferring ([D-Trp(32)]NPY and hPP) peptide agonists, evoke similar levels of inhibition at excitatory CA3 synapses in hippocampal slices from wild-type control mice (WT). In contrast, NPYergic inhibition of excitatory CA3 synaptic transmission is absent in mice lacking the Y5R subtype (Y5R KO). In both analyses of evoked population spike activity and spontaneous excitatory postsynaptic synaptic currents (EPSCs), NPY agonists induced powerful inhibitory effects in all hippocampal slices from WT mice, whereas these peptides had no effect in slices from Y5R KO mice. In slices from WT mice, NPY (and NPY receptor-preferring agonists) reduced the frequency of spontaneous EPSCs but had no effect on sEPSC amplitude, rise time, or decay time. Furthermore, NPYergic modulation of spontaneous EPSCs in WT mice was mimicked by bath application of a novel Y5R-selective peptide agonist ([cpp]hPP) but not the selective Y2R agonist ([ahx(5-24)]NPY). In situ hybridization was used to confirm the presence of NPY, Y2, and Y5 mRNA in the hippocampus of WT mice and the absence of Y5R in knockout mice. These results suggest that the Y5 receptor subtype, previously believed to mediate food intake, plays a critical role in modulation of hippocampal excitatory transmission at the hilar-to-CA3 synapse in the mouse.
 ...
PMID:Y5 receptors mediate neuropeptide Y actions at excitatory synapses in area CA3 of the mouse hippocampus. 1178 71


<< Previous 1 2 3 4 5 6 7 Next >>