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)

We performed studies to determine the anatomical regions and chemical phenotypes of neurons within the rat medulla oblongata activated by pentylenetetrazole-induced seizures. Activated cells were identified by their expression of the c-fos gene, detected by in situ hybridization for c-fos mRNA and immunocytochemistry for Fos protein. Activated cells were located predominantly in nucleus tractus solitarius (NTS), with c-fos mRNA appearing within 20 min after seizures (peak at 1-2 h), followed by Fos immunoreactivity visible at 1 h (peak at 2-4 h). Neither nonspecific noxious stimulation by intraperitoneal injection of saline nor brief exposure to hypoxic or hypercapnic gas mixtures to stimulate chemoreceptors reproduced this pattern of labeling. Prodynorphin or proenkephalin mRNA, detected by in situ hybridization, was colocalized with Fos immunoreactivity in many NTS cells. Thus, seizures activate neuronal pathways in the medulla oblongata which express genes for endogenous opioids. Potential long-term effects of seizures are suggested by the in situ hybridization finding that NTS prodynorphin mRNA increased 24 h after seizures compared to control levels.
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PMID:Activation of the c-fos gene in prodynorphin- and proenkephalin-expressing cells of nucleus tractus solitarius after seizures. 795 42

The effect of the nitric oxide synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME, 2 and 10 mg/kg i.p.) on behavioral and biochemical changes induced by single and repeated administration of cocaine (45 mg/kg/day, i.p., for 5 days) was investigated in mice. Repeated cocaine produced a progressive increase in the intensity of seizures (a ca. 300% increase in the seizure score on day 5, as compared to day 1), this effect being associated with the enhancement of the proenkephalin mRNA level (ca. 240%) in the hippocampal dentate gyrus. L-NAME had no influence, but when used jointly with cocaine, it markedly attenuated both behavioral and biochemical effects of repeated cocaine. These data suggest that the nitric oxide pathway is involved in the progressive increase in excitability of the central nervous system after repeated cocaine administration.
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PMID:The effects of cocaine-induced seizures on the proenkephalin mRNA level in the mouse hippocampus: a possible involvement of the nitric oxide pathway. 802 98

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

We have previously shown that dextromethorphan (DM) antagonizes kainic acid (KA)-induced neurotoxicity. Accumulating evidence indicates that the induction of seizure activity causes profound alterations in the levels of hippocampal opioid peptide mRNA. The present study was performed to further explore the effect of DM on KA-induced seizures as measured by hippocampal opioid peptide mRNA levels. Both Northern blot and in situ hybridization methods were used to examine the proenkephalin (PENK) and prodynorphin (PDYN) mRNA levels in the rat hippocampus. The robust seizure activity induced by KA correlated with a significant increase in hippocampal opioid peptide mRNA levels. Pretreatment of rats with DM decreased hippocampal PENK and PDYN mRNA levels and seizure activity induced by KA. Hippocampal PDYN mRNA levels fell quickly but PENK mRNA levels fell rather slowly, indicating that the PENK and PDYN mRNAs are differentially regulated. Our results demonstrate that DM modulates opioid peptide gene expression induced by KA, and that DM protects against KA-induced seizures.
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PMID:Dextromethorphan blocks opioid peptide gene expression in the rat hippocampus induced by kainic acid. 917 61

Neuronal plasticity plays a very important role in brain adaptations to environmental stimuli, disease, and aging processes. The kainic acid model of temporal lobe epilepsy was used to study the long-term anatomical and biochemical changes in the hippocampus after seizures. Using Northern blot analysis, immunocytochemistry, and Western blot analysis, we have found a long-term elevation of the proconvulsive opioid peptide, enkephalin, in the rat hippocampus. We have also demonstrated that an activator protein-1 transcription factor, the 35-kDa fos-related antigen, can be induced and elevated for at least 1 year after kainate treatment. This study demonstrated that a single systemic injection of kainate produces almost permanent increases in the enkephalin and an activator protein-1 transcription factor, the 35-kDa fos-related antigen, in the rat hippocampus, and it is likely that these two events are closely associated with the molecular mechanisms of induction of long-lasting enhanced seizure susceptibility in the kainate-induced seizure model. The long-term expression of the proenkephalin mRNA and its peptides in the kainate-treated rat hippocampus also suggests an important role in the recurrent seizures of temporal lobe epilepsy.
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PMID:A single dose of kainic acid elevates the levels of enkephalins and activator protein-1 transcription factors in the hippocampus for up to 1 year. 925 98

To determine the possible role of cyclooxygenase/lipoxygenase pathway in the regulation of proenkephalin (proENK) and prodynorphin (proDYN) gene expression induced by kainic acid (KA) in rat hippocampus, the effects of esculetin, aspirin, or phenidone on the seizure activity, proENK and proDYN mRNA levels, and the level of fos-related antigene (Fra) protein induced by KA in rat hippocampus were studied. Esculetin (5 mg/kg), aspirin (15 mg/kg), or phenidone (50 mg/kg) was administered orally five times every 12 h before the injection of KA (10 mg/kg, i.p.). Seizure activity induced by KA was significantly attenuated by phenidone. However, neither esculetin nor aspirin affected KA-induced seizure activity. The proENK and proDYN mRNA levels were markedly increased 4 and 24 h after KA administration. The elevations of both proENK and proDYN mRNA levels induced by KA were inhibited by pre-administration with phenidone, but not with esculetin and aspirin. ProENK-like protein level increased by KA administration was also inhibited by pre-administration with phenidone, but not with esculetin and aspirin. The increases of proENK and proDYN mRNA levels induced by KA were well correlated with the increases of Fra protein level. Additionally, the induction of Fra protein was inhibited by pre-administration with phenidone, but not with esculetin and aspirin. The results suggest that blockade of both cyclooxygenase and lipoxygenase pathways appears to be responsible for increases of proENK and proDYN mRNA levels induced by KA via inhibiting the induction of Fra protein in rat hippocampus.
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PMID:Phenidone blocks the increases of proenkephalin and prodynorphin gene expression induced by kainic acid in rat hippocampus: involvement of Fos-related antigene protein. 951 84

For a long time Fos has been proposed to play some role in regulation of the proenkephalin (PENK) and prodynorphin (PDYN) gene expression. In recent years, however, evidence has accumulated that the transcription of both genes in several brain regions in vivo is transactivated by the transcription factor CREB rather than by Fos. In the present study, involvement of Fos in the mechanism of the PENK and PDYN gene induction in the hippocampal dentate gyrus during seizures elicited by kainic acid was studied using a knock-down technique. Pretreatment with an antisense oligonucleotide complementary to c-fos mRNA did not influence the kainic acid-elicited convulsions. It inhibited, by about 50%, the induction of Fos protein in the dentate gyrus during seizures. The subsequent induction of PENK and PDYN mRNAs was reduced by more than 60% by the c-fos antisense oligonucleotide, while constitutive expression of three other genes (alpha-tubulin, NMDA receptor-1, and GS protein alpha-subunit) was not affected. The obtained results support the view that Fos may be involved in regulation of the PENK and PDYN gene expression in the dentate gyrus during seizures, which further suggests that the mechanisms triggering the up-regulation of both these genes in the dentate gyrus may differ from these working in other brain regions, such as the striatum and hypothalamus.
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PMID:Evidence for Fos involvement in the regulation of proenkephalin and prodynorphin gene expression in the rat hippocampus. 955 37

Systemic administration of kainic acid (KA), a glutamate receptor agonist, causes robust seizures and has been used as an excellent rodent model for human temporal lobe epilepsy. Recently, we have demonstrated that a single injection of KA increases the steady-state levels of proenkephalin (PENK) mRNA in the rat hippocampus for at least one year. However, the molecular mechanisms underlying this long-term increase in PENK mRNA levels have not been clearly defined. To determine the possible involvement of the Sp-1 transcription factors in this regulation, electrophoresis mobility-shift assays were used to study the expression of Sp-1 factors in the hippocampus after KA treatment. The results showed that there are long-lasting increases in Sp-1 DNA-binding activity. The Sp-1 DNA-binding complexes were only competed by the non-radioactive Sp-1 element and not by ENKCRE2, AP-1 or CRE elements, indicating the specificity of Sp-1 DNA-binding activity. Since the expression of Sp-1 parallels the time course of long-lasting increase in the expression of PENK mRNA and mossy fiber sprouting after KA treatment, we hypothesize that the increase in Sp-1 activity may be associated with the long-term changes in the plasticity of hippocampal function after KA-induced seizures.
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PMID:Long-term increase of Sp-1 transcription factors in the hippocampus after kainic acid treatment. 1035 Jun 46

The development of epilepsy and a progressive increase in susceptibility to seizures may involve changes in inhibitory and excitatory systems from the beginning of the process. The present study was focused to analyze the opioid peptide changes induced by a chemical sub-convulsant stimulation. Experiments were carried out to determine opioid peptide release, mu receptor binding and proenkephalin expression in rat brain, as well as nociceptive responses, following the administration of a sub-convulsant dose of pentylenetetrazol (PTZ) (30 mg/kg, i.p.). Membrane binding experiments revealed reduced number of mu binding sites (Bmax) in cortex and amygdala, but not in striatum and hippocampus, an effect that was evident only 24 h, but not 28 days, after PTZ treatment. In situ hybridization experiments suggested a significant enhancement of proenkephalin mRNA expression in specific brain regions 24 h after PTZ treatment. Microdialysis combined with a universal opioid peptide radioimmunoassay revealed extracellular opioid peptide levels to be elevated in the amygdala (137%) 90 min after PTZ administration. Evaluation of nociceptive responses using the Randall-Selitto test showed an analgesic effect short term (30-90 min) after PTZ injection. Collectively, these data provide evidence for a significant activation of opioid peptide systems as a consequence of the administration of a sub-convulsant dose of PTZ. These neurochemical changes may play an important role in the progression of epileptogenesis.
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PMID:Opioid peptide systems following a subconvulsant dose of pentylenetetrazol in rats. 1051 Sep 80

Alterations in the opioid system in the hippocampal formation and some of the possible functional consequences were investigated in adult male rats that were prenatally exposed to either saline or morphine (10 mg/kg twice daily on gestational days 11-18). In situ hybridization and Northern blots were used to measure proenkephalin and prodynorphin mRNA, and radioimmunoassays quantified proenkephalin- and prodynorphin-derived peptide levels in the dentate gyrus, CA3, and CA1 subfields of the hippocampal formation. Prenatal morphine exposure in male rats decreases proenkephalin and increases prodynorphin mRNA selectively in the granule cell layer of the dentate gyrus. Similarly, met-enkephalin peptide levels are decreased and dynorphin B peptide levels are increased in the dentate gyrus but not CA3 or CA1 of prenatally morphine-exposed males. In addition, there are decreases in dynorphin-derived peptides in the CA3 subfield. Receptor autoradiography revealed increases in the density of micro but not delta receptor labeling in discrete strata of specific hippocampal subfields in morphine-exposed males. Because alterations in the hippocampal opioid system suggest possible alterations in the excitability of the hippocampal formation, changes in opioid regulation of seizures were examined. Morphine exposure, however, does not alter the latency to onset or number of episodes of wet dog shakes or clonic seizures induced by infusion of 10 nmol [D-Ala2, MePhe4, Gly-ol5]enkephalin into the ventral hippocampal formation. Interestingly, a naloxone (5 mg/kg) injection 30 min before bicuculline administration reverses the increased latency to onset of clonic and tonic-clonic seizures in morphine-exposed males. Thus, the present study suggests that exposure of rats to morphine during early development alters the hippocampal opioid system, suggesting possible consequences for hippocampal-mediated functions.
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PMID:Field-specific changes in hippocampal opioid mRNA, peptides, and receptors due to prenatal morphine exposure in adult male rats. 1520 53


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