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 bmi-1 proto-oncogene has been implicated in B-cell lymphomagenesis in E mu-myc transgenic mice. Distinct domains of the Bmi-1 protein are highly conserved within the Drosophila protein Posterior Sex Combs, a member of the Polycomb group involved in maintaining stable repression of homeotic genes during development. We have inactivated the bmi-1 gene in the germ line of mice by homologous recombination in ES cells. Null mutant mice display three phenotypic alterations: (1) a progressive decrease in the number of hematopoietic cells and an impaired proliferative response of these cells to mitogens; (2) neurological abnormalities manifested by an ataxic gait and sporadic seizures; and (3) posterior transformation, in most cases along the complete anteroposterior axis of the skeleton. The observations indicate that Mbi-1 plays an important role in morphogenesis during embryonic development and in hematopoiesis throughout pre- and postnatal life. Furthermore, these data provide the first evidence of functional conservation of a mammalian Polycomb group homolog.
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PMID:Posterior transformation, neurological abnormalities, and severe hematopoietic defects in mice with a targeted deletion of the bmi-1 proto-oncogene. 792 65

Topographic patterns of pure-tone responses in inferior colliculus (IC) of Wistar rats were mapped using immunohistochemical staining for the nuclear protein Fos, the translation product of the c-fos proto-oncogene. Patterns were compared in ICs of immature and mature rats and in mature rats which experienced auditory deprivation beginning on day 14, an age near the developmental onset of hearing. Neonatal hearing losses, caused here by exposure to potentially deafening noise, are known to result in audiogenic seizure susceptibility in neonatal rats. These seizures can be triggered only by high-frequency stimuli and are believed to be initiated in IC. Thus, it seemed possible that susceptibility might depend on derangements of topographic frequency representation due to neonatal auditory deprivation. The band-like frequency-response domains, characteristic of adult IC, were found to be poorly differentiated in ICs of immature rats. On day 12, only lower-frequency stimuli induced discrete bands of Fos immunoreactivity while responses to higher frequencies remained exceptionally diffuse within ventral portions of IC. Only after day 24 did responses to the highest frequencies also appear mature. Furthermore, most significantly, adult rats which were transiently deafened on day 14, retained the more voluminous response patterns which were characteristic of immature IC. Because frequency selectivity in cochlea also develops by a low-to-high frequency sequence, results are consistent with a hypothesis that topographic organization arises in IC by an activity-dependent process. Whereas neonatal noise exposure also conferred audiogenic seizure susceptibility, it appears the arrest of tonotopic organization of IC is the probable basis of this reflex epilepsy.
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PMID:Development of frequency-selective domains in inferior colliculus of normal and neonatally noise-exposed rats. 815 11

Treatment of rats with the central thiamine antagonist, pyrithiamine, results in severe neurological symptoms such as ataxia and convulsions. Induction of proto-oncogene c-fos expression, often related to seizure activity, has been detected in the brains of thiamine-deficient rats by means of Northern blot analysis and in situ hybridization. Region-selective increases of lactate observed following thiamine deficiency development are largely coincident with histologically vulnerable regions. When thiamine-deficient rats were treated with the calcium channel blocker, nicardipine, lesions associated with thiamine deficiency did not appear and there was no induction of c-fos mRNA expression. This suggests a neurocytoprotective role of nicardipine to neuronal cell damage in thiamine-deficient encephalopathy.
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PMID:Proto-oncogene c-fos induction in thiamine-deficient encephalopathy. Protective effects of nicardipine on pyrithiamine-induced lesions. 822 66

The mas proto-oncogene encodes a seven membrane-spanning G-protein-coupled receptor which is activated by angiotensins. In the postnatal and adult rat, mas mRNA is specifically expressed at high levels in hippocampal neurons. We report here using in situ hybridization and RNase protection that brief seizure episodes lead to a significant and transient increase in mas mRNA in the hippocampus. Increased levels of mas transcripts were detected 2, 4, and 6 h following seizure. By 24 h post seizure, baseline levels were detected. The presumed subsequent increase of the mas receptor protein may contribute to anatomical and physiological plasticity that is associated with intense activation of hippocampal pathways.
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PMID:Expression of the mas proto-oncogene in the rat hippocampal formation is regulated by neuronal activity. 823 33

The present study was directed at evaluating the possible involvement of protein synthesis in excitotoxin-induced neuronal damage and prolonged expression of the proto-oncogene, c-fos. Kainic acid-induced seizure activity elicited varying degrees of neuronal damage and cell loss in selectively vulnerable regions of the adult rat limbic system. Pretreatment with cycloheximide, a protein synthesis inhibitor, did not alter behavioral seizure characteristics, but markedly attenuated damage to susceptible neuronal populations. A prolonged increase in c-fos mRNA was observed by in situ hybridization up to 16 h after the onset of seizures in regions exhibiting neuronal death. Pretreatment with cycloheximide did not affect the transient induction of c-fos observed in numerous structures, but significantly reduced the prolonged expression of c-fos mRNA in kainate-vulnerable regions. Despite producing massive seizure activity, systemic kainic acid administration during the early postnatal period did not induce any neuronal death, and did not result in prolonged c-fos expression in any brain structures. The developmental onset of selective neuronal vulnerability coincided with that of prolonged c-fos expression in susceptible neuronal populations. In adult rats, seizure activity induced by pentylenetetrazole did not produce neuronal damage nor did it produce prolonged c-fos expression. These results not only demonstrate that kainate-induced neurotoxicity and the prolonged expression of c-fos are both prevented by cycloheximide, but also strengthen idea that prolonged c-fos expression is a marker of neuronal death.
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PMID:Cycloheximide prevents kainate-induced neuronal death and c-fos expression in adult rat brain. 829 88

The expression of the c-fos proto-oncogene, as estimated by immunohistochemistry of the FOS nuclear protein, was studied in both focal and generalized seizures induced in rats by systemic administration of pilocarpine. Focal seizures, as indicated by the occurrence of stereotyped oral movements, chewing and sniffing, were evoked by either a subconvulsant dose of pilocarpine (200 mg/kg) or the association of a convulsant dose of pilocarpine (400 mg/kg) with SCH 23390, a selective D-1 dopamine receptor antagonist. This seizure pattern resulted in FOS accumulation in certain limbic areas, namely, the piriform cortex, amygdala, and olfactory tubercle. On the other hand, in rats developing generalized seizures, accumulation of FOS was also found in hippocampus, cingulate cortex, frontal cortex, striatum, accumbens, as well as in certain thalamic nuclei. Generalized seizures, including motor limbic seizures and status epilepticus, were induced by either a convulsant dose of pilocarpine (400 mg/kg) or a low dose of pilocarpine (15-200 mg/kg) combined with either lithium or the D-1 selective agonist SKF 38393. These findings indicate a close correlation between the sequence of behavioural alterations induced by pilocarpine and the proto-oncogene activation. The results provide the basis for mapping the areas of origin and the pathways of generalization of seizure activity. As shown by the effects of dopamine receptor agonists and antagonists, the process of generalization appears to be controlled by the dopamine system.
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PMID:Expression of c-fos protein in the experimental epilepsy induced by pilocarpine. 851 14

We previously reported that Qingyangshen (QYS), a traditional Chinese medicine with antiepileptic property, had therapeutic effect on kainic acid (KA) induced experimental seizures (see JTCM 13 (4): 281-286, 1993 for reference). To investigate the mechanisms underlying the anticonvulsant action of QYS, we analyzed the modulatory effect of QYS on rat hippocampal c-fos proto-oncogene expression during KA-induced epileptogenesis in this and the following paper. The expression of hippocampal c-fos gene during KA-induced seizures were examined first. Rats were intraperitoneally injected with kainic acid (KA, 12 mg/kg) and hippocampal c-fos mRNA level was determined by Northern blot analysis during both acute (within one day after KA injection) and chronic (15 days after KA treatment) seizures. A mild increase in hippocampal c-fos mRNA level was observed 30 min after KA injection (being 1.98 +/- 0.70 times of control level), which corresponded temporally to the occurrence of the first limbic seizures. There was an 11.02 +/- 3.33 fold maximal induction of c-fos mRNA at 2 h after KA administration, which remained relatively stable even when behavioral seizures continued to aggravate 4 h after KA treatment. Twelve hours after KA administration, c-fos mRNA in the hippocampus returned to control level when acute seizures began to gradually disappear. In contrast, the induction of hippocampal c-fos mRNA during chronic seizures was inhibited significantly, being reduced by 55.40% compared to control. This suggested that c-fos is in different functional states at acute and chronic stages of epileptogenesis induced by KA.
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PMID:Studies of qingyangshen (I): Differential expression of hippocampal c-fos proto-oncogene during kainic acid induced acute and chronic seizures. 870 12

The time course of induction of the proto-oncogene c-fos and the inducible heat shock hsp70 gene was studied from 5 minutes to 24 hours at both transcriptional (c-fos and hsp70 mRNA) and translational levels (C-FOS and HSP72 proteins) in the rat hippocampus and piriform cortex (Pir) after soman-induced seizures. Induction of c-fos was noticed as early as 5 minutes after seizures onset in all fields of hippocampal formation (CA1, CA3, CA4, and dentate gyrus) and in piriform cortex. The most intense induction was observed in piriform cortex. A sustained activation of c-fos occurred in Pir and in CA1, CA3, and CA4 areas of hippocampus. Nevertheless, histological analysis showed rare affected neurons in CA4, whereas damage was severe in Pir and in CA1 and CA3 hippocampal subfields. Induction of hsp70 mRNA occurred but was delayed in all areas previously exhibiting c-fos expression. Nevertheless HSP72 protein was never expressed in the structures where injury was high (i.e., CA1 and piriform cortex) and mainly occurred in the less damaged structure (i.e., CA4 area of hippocampus). Regional expression of glial fibrillary acidic protein mRNA was also studied in order to exclude an astroglial origin of the c-fos and hsp70 gene inductions. Our results demonstrated that after soman induced-seizures 1) there was no strict correlation between time course or intensity of neuronal c-fos induction and subsequent neuropathology, and 2) the most lesioned areas did not express HSP72 protein in spite of intense mRNA induction, suggesting that transcriptional and translational events for hsp70 gene might vary according to the severity of seizure insult.
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PMID:Time course and regional expression of C-FOS and HSP70 in hippocampus and piriform cortex following soman-induced seizures. 887 16

Activation of the proto-oncogene c-fos in the brain was described initially almost a decade ago and represents one of the most studied immediate early genes in the brain. Transient c-fos expression in the central nervous system was first observed after seizure activity and following noxious stimulation in the spinal cord. Since then, multiple studies have shown that different stimuli can induce c-fos expression. Seizure activity induces rapid and transient expression of c-fos in hippocampal structures. Similarly, transient activation of c-fos follows cortical brain injury in a pattern that resembles that of spreading depression. Many other stimuli have been shown to induce the expression of this proto-oncogene in the brain and c-fos immunostaining and in situ hybridization are now used to map brain metabolism under different physiological and non-physiological conditions. Here we review the variety of inducible patterns of c-fos expression in the brain.
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PMID:Activation of c-fos in the brain. 897 79

The ventrolateral periaqueductal gray is implicated as a component of the neuronal network for audiogenic seizure. This implication is based on immunocytochemical labeling of the proto-oncogene, c-fos, and microinjection studies in the severe substrain of genetically epilepsy-prone rats that exhibits tonic seizures. The present study examines changes in acoustically evoked neuronal responses within the periaqueductal gray in the awake and behaving genetically epilepsy-prone rat as compared to normal Sprague Dawley rats. Two populations of neuronal response were observed in the periaqueductal gray of both genetically epilepsy-prone and normal rats. Most of the neurons exhibited long latencies (>10 ms) and lower thresholds, and were more responsive to the acoustic stimulus. The remainder of the periaqueductal gray neurons exhibited short latencies (<10 ms) and higher thresholds, and exhibited minimal responsiveness to the acoustic stimulus. The mean threshold of periaqueductal gray acoustically evoked neuronal firing of short-latency neurons was significantly higher than normal in the genetically epilepsy-prone rat. The number of acoustically evoked action potentials was significantly elevated in the genetically epilepsy-prone rat, particularly at the highest acoustic intensity and at a repetition rate of 1/2 s. In the genetically epilepsy-prone rat, the number of action potentials exhibited adaptation (habituation) at 1/s as compared to 1/2 s across stimulus intensities. Habituation in normal rats was observed primarily at high intensities (95 dB sound pressure level or above). During wild running and tonic seizures in the genetically epilepsy-prone rat, periaqueductal gray neurons. which had diminished firing rates due to habituation, exhibited a tonic firing pattern. Just (1-5 s) prior to the onset of tonic convulsive behaviors, an increase in the rate of periaqueductal gray tonic firing was observed. These patterns of abnormal neuronal firing suggest that periaqueductal gray neurons may be involved in generation of the tonic seizure behavioral component of audiogenic seizure in the genetically epilepsy-prone rat, which will need confirmation in other audiogenic seizure models.
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PMID:Periaqueductal gray neurons exhibit increased responsiveness associated with audiogenic seizures in the genetically epilepsy-prone rat. 953 30


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