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)

The present study examined the response of immediate early genes following kainic acid induced seizures in mice lacking the alpha and delta isoforms of CREB. mRNA levels for c-fos, c-jun, and Krox-24 were measured following limbic seizure activity and were found to be induced in wild type as well as CREB mutant mice. This effect was also seen for these three mRNAs at the protein level as well as for FOS-B. Furthermore the time course of expression of FOS, JUN, KROX-24, and FOS-B proteins were essentially the same in CREB mutant mice as compared to wild-type controls. These data suggest that CREB alpha and delta are not required for the induction of immediate early genes following pharmacologically induced seizures.
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PMID:Effects of kainic acid induced seizures on immediate early gene expression in mice with a targeted mutation of the CREB gene. 755 95

Transcription factors are regulatory proteins that modify gene expression. Any cellular function requiring alterations in mRNA levels depends upon these factors. The CNS, AP-1 (activator protein-1; c-fos and fos-related antigens plus jun-related factors) and CREB (cAMP responsive element binding protein) families of transcription factors have been extensively studied. The DNA binding complex is composed of dimers formed between the AP-1 and CREB factors and binding specificity is dictated by which proteins comprise the complex. Whereas the AP-1 factors are inducible, CREB and related proteins are constitutive and regulate gene transcription through phosphorylation. Due to seizure activity, many AP-1 factors are induced, but rapidly return to basal levels. However, if neuronal death occurs, fos-related antigens of 35 kDa persist for an extended period and may be involved in regulating genes related to neuronal plasticity. Similar factors are expressed after chronic drug treatment indicating a role in drug tolerance. However, during early CNS development, elevated AP-1 DNA binding consisting of c-jun and CREB occurs in every brain region and is inversely related to the degree of maturation of a particular brain area. These transcription factors are important for gene regulation during CNS dysfunction and development and those present specify which genes are activated.
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PMID:AP-1 transcription factor complexes in CNS disorders and development. 756 34

A number of conditions associated with persistent excitation such as electrically and chemically-induced seizures cause a rapid increase in the expression of immediate early genes (IEG) such as c-fos. In this study the time-course of induction of c-jun, jun-B and zif 268 mRNA by kainate was characterized in rat cerebral cortex and compared to that of c-fos mRNA induction. Unilateral injection of kainate into the nucleus basalis caused a significant induction of c-jun mRNA in cerebral cortex from 4 hr which was maximal at 8 hr, being 3 times greater in ipsilateral cortex than in control cortex. This pattern was also shown for jun-B and was similar, but of small magnitude, to that obtained with c-fos mRNA, with a maximal increase at 8 hr, whilst the maximal induction of zif-268 mRNA preceded these responses occurring at 4 hr. A marked difference was seen in duration in the c-jun induction which was maintained at a high level for at least 24 hr. Treatment of animals with MK-801 (within 30 min of injection of kainate) or dexamethasone (2-30 mg/kg) at the time of kainate injection significantly attenuated the response. The induction of c-fos mRNA by kainate injection was most sensitive to dexamethasone (2 mg/kg), whereas a higher dose (30 mg/kg) was required to attenuate the induction of zif-268 mRNA. These results show that a time-dependent and co-ordinated induction of c-fos, c-jun, jun-B and zif-268 mRNA in cerebral cortex occurs in response to the persistent excitation caused by excitotoxin injection which is mediated by glutamate and shows a differential sensitivity to dexamethasone.
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PMID:Differential temporal patterns of expression of immediate early genes in cerebral cortex induced by intracerebral excitotoxin injection: sensitivity to dexamethasone and MK-801. 756 87

The present study examines the influence of electroconvulsive seizure (ECS), as well as several antidepressant drug treatments, on the induction of c-fos mRNA in response to acute restraint stress. Acute (45-minute) restraint stress resulted in five- to sixfold elevation of c-fos mRNA levels in rat frontal cortex. Chronic administration of ECS significantly decreased the induction of c-fos mRNA levels in response to acute restraint stress, and this effect was observed after chronic (6 to 9 days) but not acute (1 or 3 days) of ECS treatment. In addition, c-fos induction in response to acute restraint stress was down-regulated by chronic, but not acute, administration of tranylcypromine or imipramine, two drugs that nonselectively increase synaptic levels of norepinephrine and serotonin by inhibition of monoamine oxidase or neurotransmitter reuptake, respectively. Moreover, chronic administration of desipramine or sertraline, selective re-uptake inhibitors of norepinephrine, or serotonin, respectively, also significantly down-regulated the induction of c-fos mRNA in response to restraint stress. Chronic administration of ECS, tranylcypromine, or imipramine also decreased stressed-induced levels of NGFI-A mRNA, another immediate early gene transcription factor, whereas levels of c-jun mRNA were not influenced by either stress or antidepressant treatments. The results demonstrate that chronic, but not acute, administration of ECS and several different classes of antidepressant drugs down-regulates stress-induced levels of c-fos mRNA, suggesting that this effect may be a common, postreceptor action of antidepressant treatments.
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PMID:Chronic antidepressant treatment down-regulates the induction of c-fos mRNA in response to acute stress in rat frontal cortex. 761 55

Kainic acid-induced seizures in the rat brain cause severe brain damage that is thought to result, in part, from oxidative stress. In this study, we examine the consequences of systemic administration of kainic acid on expression of several genes that encode proteins thought to play roles in protection from oxidative stress, including metallothionein-I, and -III. Kainic acid causes an increase in metallothionein-I and heme oxygenase-I mRNAs, as well as an increase in c-fos, heat shock protein-70, and interleukin-1 beta mRNAs. The induction of these mRNAs is seizure dependent, and is greater in brain areas with extensive damage (e.g. piriform cortex) than in areas with minimal damage (e.g. frontal cortex and cerebellum). In contrast, little or no change in mRNA for metallothionein-III, manganese superoxide dismutase, copper-zinc superoxide dismutase, glutathione-s-transferase ya subunit or glutathione peroxidase occur. The prolonged and robust concordant induction of the metallothionein-I and heme oxygenase-I genes may reflect the oxidative stress produced by kainic acid-induced seizures. In addition, the induction of interleukin-1 beta gene expression suggests an inflammatory response in brain regions damaged by kainic acid-induced seizures. Delineating the regulation of genes associated with oxidative and inflammatory responses can contribute to a fuller understanding of seizures and associated brain damage.
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PMID:Temporalspatial patterns of expression of metallothionein-I and -III and other stress related genes in rat brain after kainic acid-induced seizures. 765 48

The induction of the proto-oncogene c-fos has been used extensively to identify spatially distributed neural systems activated by seizures. The substantia nigra pars reticulata (SNpr) has been implicated as a critical structure in neural networks involved in the modulation of seizure expression, yet the SNpr has not been reported to express Fos following seizures induced in a variety of seizure paradigms. In this study we determined whether (1) the temporal characteristics of Fos induction in the SNpr were different than those of other brain areas following kindled seizures, (2) neurons in the SNpr possess the cellular machinery to express Fos, (3) Fos can be induced in SNpr by direct electrical stimulation, and (4) Fos expression is induced in the SNpr following kainate or pilocarpine-induced status epilepticus. Results indicate that Fos is not induced in SNpr at any time point (1-12 h) after kindled seizures, and that serum response factor, a constitutively expressed nuclear protein necessary for Fos expression, is present in SNpr neurons. Results further indicate that Fos expression in the SNpr is induced following either direct electrical stimulation or pilocarpine status, but not status elicited by kainate. We conclude that, in so far as the SNpr represents a critical structure for modulating seizure expression, seizure activity does not represent a sufficient stimulus to induce Fos in SNpr neurons. Further, the neural networks defined by Fos expression following seizure may be incomplete, and should be interpreted conservatively.
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PMID:The substantia nigra pars reticulata, seizures and Fos expression. 771 58

Focal seizures in rats were elicited by electrical stimulation (using parameters necessary for induction of kindling) of the amygdala or two different sites of the piriform cortex, including the previously described 'area tempestas' [26]. Although seizures were behaviorally and electrophysiologically identical, a different pattern of induction of the proto-oncogene c-fos was found. Only the ipsilateral piriform cortex showed strong immunohistochemical labeling of Fos protein, regardless of stimulation site, while the hippocampus was not labeled after focal seizures. It is concluded that the piriform cortex is the epileptogenic focus of limbic seizures, at least during the first stages of electrical kindling.
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PMID:Strong induction of c-fos in the piriform cortex during focal seizures evoked from different limbic brain sites. 774 27

In the past several years a great deal of evidence has accumulated linking neuronal activation events to the regulation of gene expression. We have pursued an analysis of c-fos regulation in the nervous system to elucidate the molecular mechanisms involved in stimulus-transcription coupling. The c-fos gene can be viewed as an archetype of the set of cellular immediate-early genes encoding transcription factors. These genes are believed to function in coupling short-term signals elicited by extracellular to long-term changes in cellular phenotype by orchestrating alterations in target gene expression. Several animal seizure models have been used to demonstrate the activation of gene expression in specific populations of neurons. Using a transgenic mouse approach, based on a foslacZ fusion gene, we now demonstrate an association between c-fos expression and cell death in the nervous system. A delayed and protracted induction was observed following surgical lesion and in response to neurotoxin exposure. This system allows us to determine, for the first time, the DNA regulatory sequences that are responsible for the induction of gene expression in neurons in vivo. Furthermore, foslacZ transgenic mice provide a unique resource for identifying cell populations that respond to specific stimuli or that are susceptible to particular toxins.
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PMID:Fos: an immediate-early transcription factor in neurons. 777 73

The present study was designed to determine if and to what extent somatostatin (SST) synthesizing neurons of the hippocampal formation are activated during seizures, elicited through kindling of the perforant pathway. Tissue was used and analyzed from animals which had experienced a single after discharge, or a stage 3 or stage 5 seizure. The protein expression of the oncogene c-fos in activated, depolarizing neurons was utilized to identify seizure-activated SST-synthesizing neurons. Combined immunocytochemical and in situ hybridization methods were used to identify these double-labeled, Fos protein, and SST mRNA-containing neurons. The results were quantified and compared across seizure stages. The resulting data demonstrate that at every stage of seizure development, a majority of SST-synthesizing neurons is activated, but that these activated SST mRNA-containing neurons represent only a minority of all seizure-activated, Fos-expressing neurons in the hippocampal formation. The data further reveal a numerical hierarchy in which the majority of double-labeled neurons is present in the hilus of the dentate, followed by the stratum oriens of CA1. It is concluded that SST-synthesizing neurons represent an integral component of the kindling activated neuronal network and, since the SST synthesizing neurons represent the minority of all seizure-activated neurons in the hippocampal formation, that this neuronal network is likely to be of considerable neurochemical complexity.
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PMID:Activation of somatostatin-synthesizing neurons in the hippocampal formation through kindling-induced seizures. 778 45

Previously, we established that persistent upregulation of c-fos expression preceded kainic acid (KA)-induced neuronal death in mice. To discriminate between events that are products of the seizures elicited by KA and those that are specifically associated with its neurotoxic actions, we have examined the expression of cellular immediate-early genes (cIEGs) following KA or pentylenetetrazol (PTZ) treatment in c-fos-lacZ transgenic rats. While both chemoconvulsants elicit seizures, only KA causes selective neuronal death. Following treatment of transgenic rats with KA there was a protracted expression of Fos-lacZ that lasted for 2-3 d. In contrast, PTZ elicited a transient increase in the transgene product that lasted about 6 hr. Normally, Fos and Fos-lacZ were detected only in neuronal nuclei. However, 6 hr following kainic acid (but not PTZ) administration, beta-galactosidase activity appeared in the cytoplasm of neurons within vulnerable regions (as determined by the terminal transferase biotinylated-UTP nick end labeling (TUNEL) procedure). Like c-fos, transcripts for other cIEGs were elevated for longer periods in the KA-treated rat hippocampus. In addition, fra-1 and fra-2 were only induced in the KA-treated rat. These changes in mRNA levels were paralleled by a sustained increase in AP-1 DNA binding activity. Thus, quantitative and qualitative changes in AP-1 DNA binding complexes accompany neurotoxic cell death that are not observed following seizures.
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PMID:Kainic acid-induced neuronal death is associated with DNA damage and a unique immediate-early gene response in c-fos-lacZ transgenic rats. 779 Sep 8


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