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 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 have characterised the induction of the mitogen-inducible form of cyclooxygenase, COX-2, in the rat cerebral cortex in response to excitotoxin injection into the nucleus basalis. This model is associated with intense stimulation of the ascending pathway to the cerebral cortex, seizure activity, and subsequent ipsilateral cortical induction of various immediate early genes (IEGs), including c-fos, c-jun, and zif268, and ornithine decarboxylase enzyme activity and mRNA, all of which processes are sensitive to treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801. In this study we show that excitotoxin injection also causes a marked induction of COX-2 mRNA in ipsilateral cortex detectable at 1 h and peaking at 4 h, where COX-2 mRNA levels were 19 times those in unoperated animals. Levels of COX-2 mRNA remained significantly elevated at 24 h. The early induction of COX-2 at 1 h was also seen in sham-operated animals, but at 4 h the COX-2 mRNA level was significantly increased (4.4-fold) in animals injected with excitotoxin compared with sham-operated animals. The induction at this time point (4 h) was explored pharmacologically and found to be significantly attenuated by treatment with MK-801 (1.5 mg/kg), lamotrigine (10 mg/kg), which prevents presynaptic glutamate release by blocking voltage-sensitive Na+ channels, and the glucocorticoid dexamethasone (3 mg/kg), which has an indirect inhibitory effect on phospholipase A2 and COX activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclooxygenase-2 induction in cerebral cortex: an intracellular response to synaptic excitation. 852 90

It has been suggested that expression of the immediate early gene c-fos links fleeting changes in neuronal activity to lasting modifications of neuronal structure and function in the mammalian nervous system. To test this idea, we examined behavioral and electrophysiological indices of kindling development and kindling-induced sprouting of hippocampal granule cell axons in wild-type (+/+), heterozygous (+/-), and homozygous (-/-) mice carrying a null mutation of c-fos. The rate of kindling development was significantly attenuated in -/- compared with +/+ mice, as evidenced by both electrophysiological and behavioral measures. Kindling-induced granule cell axon sprouting as measured by the Timm stain was also attenuated in homozygous null mutants compared with +/+ mice, with an intermediate effect in +/- mice. The impairment of kindling-induced axonal sprouting in the null mutants could not be attributed to either detectable loss of dentate hilar neurons or reduced activation of the dentate granule cells by seizures. Instead, our data are consistent with the hypothesis that the null mutation of c-fos attenuates a pathological activity-determined functional plasticity (kindling development) as well as a structural plasticity (mossy fiber reorganization). We favor the hypothesis that this "fos-less phenotype" is attributable to impaired seizure-induced transcriptional activation of one or more growth-related genes.
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PMID:Null mutation of c-fos impairs structural and functional plasticities in the kindling model of epilepsy. 865 77

Activity-mediated gene expression is thought to play an important role in many forms of neuronal plasticities. We have used pentylenetetrazol-induced seizure that produces synchronous and sustained neuronal activity as a model to examine the mechanism(s) of gene activation. The transcription factor CREB (Ca2+/cAMP response element-binding protein) is thought to be necessary for long-term memory formation both in invertebrates and vertebrates. When phosphorylated on Ser133 either by cAMP-dependent protein kinase and/or Ca2+/calmodulin-dependent protein kinases, CREB increases transcription of genes containing the CRE (cAMP response element) sequence. Using an antibody that detects Ser133-phosphorylated CREB protein, we show that CREB phosphorylation is maximal between 3 and 8 min after the onset of seizure activity and declines slowly both in the hippocampus and the cortex. The total amount of CREB protein did not change at the time points examined. The increased phosphorylation of CREB protein is preceded by an increase in the amount of cAMP, suggestive of cAMP-dependent protein kinase activation, in the hippocampus and activation of Ca2+/calmodulin-dependent protein kinases in the cortex. Subsequent to CREB phosphorylation, the expression of the CRE-containing gene, c-fos, and the AP-1 complexes (heterodimers of Fos and Jun family members) is increased. These findings support the role of CREB-mediated gene expression in activity-dependent neuronal plasticities.
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PMID:Neuronal activity increases the phosphorylation of the transcription factor cAMP response element-binding protein (CREB) in rat hippocampus and cortex. 866 77

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

In situ hybridization histochemistry was used to evaluate the expression of the immediate-early gene c-fos following the induction of audiogenic seizures in adult rats with transient neonatal hypothyroidism. The rats treated with 0.02% propylthiouracil (PTU) through mother's milk during days 0-19 after delivery showed a high incidence of seizures to auditory stimulation at the age of 4 months. The significant induction of c-fos mRNA by audiogenic seizures is prominent in several brain areas including central gray, peripeduncular nucleus, inferior colliculus, septal nucleus, bed nucleus of stria terminalis, and dorsomedial hypothalamus. However, the expression of c-fos mRNA was comparable in neocortex, dorsal hippocampus and medial geniculate body between control rats and PTU-treated, seizure-induced rats. These results confirm the previous report on the c-fos expression following audiogenic seizure sensitized during development by a loud noise [20]. The present results indicate that the neonatal PTU treatment may provide a useful tool for studying the mechanism underlying the seizure susceptibility and development after maturation.
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PMID:Expression of c-fos mRNA after audiogenic seizure in adult rats with neonatal hypothyroidism. 873 71

We have reported that, after KA treatment in rats, there was first a significant increase in hippocampal c-fos expression during acute seizures and then a long-term inhibition in hippocampal c-fos expression during chronic seizures. In this experiment, we examined the modulatory effect of Qingyangshen (QYS), a traditional Chinese medicine with antiepileptic property, and diphenylhydantoin sodium (DPH) on hippocampal c-fos expression during seizures. We found that after intraperitoneal injection of QYS + DPH (15 mg/kg and 50 mg/kg respectively, q.o.d. x 6), the peak level of hippocampal c-fos mRNA induction during KA-induced acute seizures was reduced by 56.27%; while the inhibition of hippocampal c-fos expression during KA-induced chronic seizures was disinhibited to control level. It is suggested that the inhibitory effect of QYS + DPH on KA-induced seizures, chronic seizures in particular, may have much to do with its modulatory effect on hippocampal c-fos expression.
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PMID:Studies of Qingyangshen (II): modulatory effect of co-treatment with qingyangshen and diphenylhydantoin sodium on rat hippocampal c-fos expression during seizures. 875 11

In this study, Sprague-Dawley (S.D.) rats were pretreated with kainic acid (KA, 10 mg/kg, i. sc.) 72 days before either deep prepyriform cortex (DPC) kindling or injection of the same dose of KA. The results showed that such pretreatment accelerated the process of kindling, and the KA-induced seizures appeared more severe in behaviours. c-Fos-immunoreactivity (c-Fos-ir) was used to demonstrate the neuronal activity in central nervous system during the provocative dose of KA-induced seizure, as comparing with the control which received normal saline of KA 72 days ago. The results indicated that, the transmission pathways in two groups were just the same; but the time courses of c-fos and c-jun expression in KA pretreated group were accelerated asynchronously; and the synthesis of the proenkephalin mRNA in the Ent was apparently up-regulated. It is suggested that, the long-lasting increase in susceptibility to seizure induced by a single administration of KA may be related to the acceleration of the expression of c-fos/jun and the early onset of the expression of proenkephalin mRNA.
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PMID:[The effects of single administration of kainic acid on cellular signal transmission pathway and susceptibility to seizure]. 876 50

Induction of c-fos mRNA and Fos was studied in the hilus and granular layer of the dentate gyrus at various times up to 24 h after single electroconvulsive stimulation (ECS) using in situ hybridization and immunocytochemistry. In both areas of the dentate gyrus, a prominent induction of c-fos mRNA and Fos was observed. Compared to the granular layer, however, c-fos mRNA and Fos in hilar cells reached maximum later and remained elevated considerably longer. Several neurochemically distinct populations of hilar neurons have been described, some of which contain neuropeptide Y (NPY) and/or somatostatin (SS). Using double-labelling immunocytochemistry, we examined to what extent Fos was induced in these hilar neurons after ECS. Although a minor population of non-NPY non-SS cells displayed Fos induction early after ECS, prolonged induction of Fos almost exclusively occurred in NPY or SS neurons. The Fos-immunoreactive NPY or SS neurons only amounted to about 50% of the total hilar population of NPY or SS neurons. The present observations suggest that a subpopulation of hilar NPY and SS neurons may be central to the actions of electroconvulsive seizures in the dentate gyrus.
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PMID:Prolonged induction of c-fos in neuropeptide Y- and somatostatin-immunoreactive neurons of the rat dentate gyrus after electroconvulsive stimulation. 878 3

The molecular mechanisms associated with age-related alterations in the pharmacological and physiological properties of hippocampal and cortical neurons in response to chemically induced seizure are largely unknown. Administration of pentylenetetrazole (PTZ) (50 mg/kg body weight) to rats of various ages evoked tonic-colonic seizures. Using RNA gel blot analysis we found that 1 h after the onset of seizure, the mRNA for the protooncogene c-fos was increased in the hippocampus and cortex of 3-month-old rats. The levels of c-fos mRNA in the hippocampus and cortex of 3-month-old rats returned to control levels by 3 h after PTZ administration. The levels of c-fos mRNA in the hippocampus and cortex of 20-month-old and 30-month-old rats peaked at 3 h and returned to basal levels by 15 h following PTZ treatment. These results suggest that the induction of immediate-early gene expression, as exemplified by c-fos, is not impaired in the aged rat brain. However, the aged rat brain responded more slowly to chemically induced seizure and the levels of c-fos mRNA induction are decreased by about 49% in the cortex and by 27% in the hippocampus of 30-month-old rats, as compared to the levels expressed by 3-month-old rats.
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PMID:Seizure induced C-Fos mRNA in the rat brain: comparison between young and aging animals. 878 1


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