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)

The nerve growth factor-induced clone C (NGFI-C) gene encodes a zinc-finger transcription factor that is rapidly induced by nerve growth factor in rat pheochromocytoma PC12 cells and by seizure in brain. NGFI-C is closely related to the previously described early response genes, nerve growth factor-induced clone A (NGFI-A or EGR1), EGR2, and EGR3. These four early response (immediate early) proteins all contain very similar zinc-finger DNA binding domains; in addition, analysis of the non-zinc-finger region revealed that they share an additional five highly homologous subdomains, four of which are within the amino terminus. The 5' flanking region of NGFI-C contains several cAMP response elements but does not contain any serum-response elements or CArG boxes [CC(A/T)6GG], cis-acting elements commonly involved in early response gene regulation. NGFI-C mRNA was detected in neural tissues of postnatal animals, but no expression was found in rat embryos. In situ hybridization demonstrated that NGFI-C is rapidly induced in the dentate gyrus of the hippocampus after seizure, but in contrast to NGFI-A, increases in NGFI-C mRNA were not detected in the overlying cortex. By using fluorescence in situ hybridization, NGFI-C was localized to human chromosome 2p13. This region contains a constitutive fragile site that is associated with chromosomal breakpoints and translocations characteristic of some chronic lymphocytic leukemias.
 ...
PMID:Neural-specific expression, genomic structure, and chromosomal localization of the gene encoding the zinc-finger transcription factor NGFI-C. 163 Nov 70

Mammalian neurons contain at least three types of excitatory amino-acid receptors, selectively activated by N-methyl-D-aspartate (NMDA) or aspartate, (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate ((S)-AMPA) and kainate. An important aspect of NMDA receptors is their regulation by a variety of factors such as glycine, Mg2+ and Zn2+ that are present in vivo. We show here that NMDA receptor responses are selectively inhibited by protons, with a 50% inhibitory concentration (IC50) that is close to physiological pH, implying that NMDA receptors are not fully active under normal conditions. (S)-AMPA and kainate responses remain unchanged at similar pH levels. Proton inhibition is voltage-insensitive and does not result either from fast channel block, a change in channel conductance, or an increase in the 50% excitatory concentration (EC50) of aspartate/NMDA or glycine. Instead, protons seem to decrease markedly the opening frequency of 30-50 pS NMDA channels, and reduce the relative proportion of longer bursts. This feature of NMDA receptors could be relevant to neurotoxic activation of NMDA receptors during ischaemia, as well as to seizure generation, as extracellular proton changes occur during both of these pathological situations. Furthermore, these results may have implications for normal NMDA receptor function as transient changes in extracellular protons occur during synaptic transmission.
 ...
PMID:Proton inhibition of N-methyl-D-aspartate receptors in cerebellar neurons. 169 70

This study was designed to identify whether synaptic reorganizations occur in epileptic human hippocampus which might contribute to feedback excitation. In epileptic hippocampi, (n = 21) reactive synaptogenesis of mossy fibers into the inner molecular layer of the granule cell dendrites was demonstrated at the light microscopic and electron microscopic levels. There was no inner molecular layer staining for mossy fibers in autopsy controls (n = 4) or in controls with neocortex epilepsy having no hippocampal sclerosis (n = 2). Comparing epileptics to controls, there were statistically significant correlations between Timm stain density and hilar cell loss. Since hilar neurons are the origin of ipsilateral projections to the inner molecular layer, this suggests that hilar deafferentation of this dendritic zone precedes mossy fiber reafferentation. Quantitative Timm-stained electron microscopy revealed large, zinc-labelled vesicles in terminals with asymmetric synapses on dendrites in the inner molecular and granule cell layers. Terminals in the middle and outer molecular layers did not contain zinc, were smaller and had smaller vesicles. These histochemical and ultrastructural data suggest that in damaged human epileptic hippocampus, mossy fiber reactive synaptogenesis may result in monosynaptic recurrent excitation of granule cells that could contribute to focal seizure onsets.
 ...
PMID:Synaptic reorganization by mossy fibers in human epileptic fascia dentata. 171 44

The possible role played by superoxide dismutase (SOD), a major defense system for counteracting the toxic effects of oxygen free radicals, in amygdaloid (AM) kindling was examined in rats. A significant increase of total SOD activity in the whole brain was observed 30 days after completion of AM kindling. Intra-AM injection of 3 ng of one of the 2 SOD enzymes present in mammalian brain, i.e. cytosolic SOD containing copper and zinc (CuZn-SOD) caused suppression of kindled seizure. These results suggest that SOD participates in the persistence of AM kindled seizure susceptibility and the initiation of kindled AM seizure.
 ...
PMID:Increased activity of superoxide dismutase in kindled brain and suppression of kindled seizure following intra-amygdaloid injection of superoxide dismutase in rats. 174 63

The mammalian central nervous system (CNS) contains an abundance of the transition metal zinc, which is highly localized in the neuronal parenchyma. Zinc is actively taken up and stored in synaptic vesicles in nerve terminals, and stimulation of nerve fibre tracts that contain large amounts of zinc, such as the hippocampal mossy fibre system, can induce its release, suggesting that it may act as a neuromodulator. The known interaction of zinc with the major excitatory and inhibitory amino-acid neurotransmitter receptors in the CNS supports this notion. That zinc has a role in CNS synaptic transmission, however, has so far not been shown. Here we report a physiological role for zinc in the young rat hippocampus (postnatal, P3-P14 days). Our results indicate that naturally occurring spontaneous giant depolarizing synaptic potentials (GDPs) in young CA3 pyramidal neurones, mediated by the release of GABA (gamma-aminobutyric acid), are induced by endogenously released zinc. These synaptic potentials are inhibited by specific zinc-chelating agents. GDPs are apparently generated by an inhibitory action of zinc on both pre- and postsynaptic GABAB receptors in the hippocampus. Our study implies that zinc modulates synaptic transmission in the immature hippocampus, a finding that may have implications for understanding benign postnatal seizures in young children suffering with acute zinc deficiency.
 ...
PMID:A physiological role for endogenous zinc in rat hippocampal synaptic neurotransmission. 184 46

Hippocampal mossy fiber zinc was examined in mice selectively bred for differences in susceptibility to handling-induced convulsions during ethanol withdrawal. The density of mossy fiber zinc in the CA3 stratum lucidum was significantly decreased in the duplicate lines of untreated withdrawal seizure prone (WSP) mice compared to untreated withdrawal seizure resistant (WSR) mice. Mossy fiber zinc densities in randomly bred control lines of mice (WSC) were intermediate to WSP and WSR mice. Serum, whole brain and whole hippocampal zinc were not significantly different between WSP and WSR mice, indicating that the reduction in the chelatable pool of hippocampal mossy fiber zinc was not a consequence of deficits in brain or whole body zinc nutrition. A highly significant correlation between hippocampal mossy fiber zinc density and handling-induced convulsion indices suggests that a reduction in mossy fiber zinc may be one contributing factor in the expression of seizure susceptibility in WSP mice.
 ...
PMID:Hippocampal mossy fiber zinc deficit in mice genetically selected for ethanol withdrawal seizure susceptibility. 186 62

Recent studies have revealed that mossy fiber axons of granule cells in the dentate gyrus undergo reorganization of their terminal projections in both animal models of epilepsy and human epilepsy. This synaptic reorganization has been demonstrated by the Timm method, a histochemical technique that selectively labels synaptic terminals of mossy fibers because of their high zinc content. It has been generally presumed that the reorganization of the terminal projections of the mossy fiber pathway is a consequence of axonal sprouting and synaptogenesis by mossy fibers. To evaluate this possibility further, the time course for development of Timm granules, which correspond ultrastructurally to mossy fiber synaptic terminals, was examined in the supragranular layer of the dentate gyrus at the initiation of kindling stimulation with an improved scoring method for assessment of alterations in Timm histochemistry. The progression and permanence of this histological alteration were similarly evaluated during the behavioral and electrographic evolution of kindling evoked by perforant path, amygdala, or olfactory bulb stimulation. Mossy fiber synaptic terminals developed in the supragranular region of the dentate gyrus by 4 d after initiation of kindling stimulation in a time course compatible with axon sprouting. The induced alterations in the terminal projections of the mossy fiber pathway progressed with the evolution of behavioral kindled seizures, became permanent in parallel with the development of longlasting susceptibility to evoked seizures, and were observed as long as 8 months after the last evoked kindled seizure. The results demonstrated a strong correlation between mossy fiber synaptic reorganization and the development, progression, and permanence of the kindling phenomenon.
 ...
PMID:Mossy fiber synaptic reorganization induced by kindling: time course of development, progression, and permanence. 188 May 49

The use of disclosing media has been recommended to enhance the fit of castings. This study evaluated the film thickness of four disclosing media: (1) disclosing wax, (2) Net spray, (3) G-C Check Fit material, and (4) Extrude polyvinylsiloxane (low viscosity) impression material. ADA Specification No. 8 for zinc phosphate cement gives a maximum film thickness for the cement that was used as the control for these four media. The results demonstrated that the film thicknesses of all four disclosing media were less than the 25 microns maximum allowed for zinc phosphate cement.
 ...
PMID:Film thickness of four disclosing media. 207 35

We have cloned NGFI-C, a nerve growth factor-induced early-response gene which encodes a Cys2/His2 zinc finger protein. RNA blot analysis demonstrates that NGFI-C mRNA is induced within minutes of stimulation of PC12 cells by nerve growth factor and is similarly activated in brain after a Metrazol-induced seizure. The cDNA sequence predicts a protein that contains three zinc fingers which show striking homology to the DNA-binding regions of three previously reported zinc finger proteins, NGFI-A, Krox-20, and the Wilms' tumor gene product. NGFI-C binds to the previously described DNA-binding site of these three proteins, which is GCGGGGGCG. Cotransfection experiments revealed that NGFI-C strongly activates transcription from this site in mammalian cells. The isolation of another early-response gene that encodes a member of the G(C/G)G or GSG element-binding family should provide an opportunity to investigate the relative contributions of a family of transcription factors to the cell's response to changes in its environment.
 ...
PMID:The early response gene NGFI-C encodes a zinc finger transcriptional activator and is a member of the GCGGGGGCG (GSG) element-binding protein family. 207 95

Male Fischer-344 rats were injected i.p. with diethyldithiocarbamate or dithizone 15 min after kainic acid (KA), s.c. Diethyldithiocarbamate and dithizone reduced both the number of wet dog shakes and the latency to onset of seizures induced by KA. Moreover, they increased the severity of seizures. These compounds may be useful tools for investigating the role of zinc in central nervous system excitatory transmission and/or convulsive phenomena.
 ...
PMID:Diethyldithiocarbamate and dithizone augment the toxicity of kainic acid. 215 90


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