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)

An in situ hybridization study showed that limbic seizures induced by kainate strongly augmented the prodynorphin and proenkephalin messenger RNA levels in granular cells of the rat hippocampal dentate gyrus. Pentylenetetrazole increased the level of proenkephalin messenger RNA, but slightly decreased that of prodynorphin messenger RNA in the dentate gyrus. Administration of kainate to rats caused a profound increase in messenger RNAs of the transcription factor genes c-fos and c-jun in the dentate gyrus, followed by an increase in the level of the transcriptional complex activator protein-1 in hippocampal neurons. Pentylenetetrazole also elevated the formation of activator protein-1, but the effect appeared earlier than that induced by kainate. Thus, recurrent limbic seizures activate both prodynorphin and proenkephalin genes, whereas generalized clonic-tonic seizures seem to decrease the prodynorphin and increase the proenkephalin gene expression in the dentate gyrus. Furthermore, our present results suggest that the transcription factors, c-fos, c-jun and activator protein-1 complex may be involved in the process of inducing the hippocampal proenkephalin gene, while these factors might be differently involved in regulation of prodynorphin gene expression.
 ...
PMID:Seizure related changes in the regulation of opioid genes and transcription factors in the dentate gyrus of rat hippocampus. 747 37

Expression of the opioid peptides dynorphin and enkephalin is altered within the first 24 h after acutely induced seizures in certain experimental models of epilepsy. Using in situ hybridization, we examined the expression of prodynorphin and preproenkephalin messenger RNA acutely following induction of kindling with recurrent seizures and in two models of chronic temporal lobe epilepsy: (i) rats fully kindled with rapidly recurring hippocampal seizures; and (ii) rats surviving after self-sustaining limbic status epilepticus induced with focal electrical stimulation of the hippocampus. In naive animals, a ventral-dorsal gradient was identified in the expression of both prodynorphin and preproenkephalin messenger RNA in the dentate gyrus and expression of prodynorphin message was demonstrated for the first time in the ventral portion of cornu Ammonis regio superior. After stimulation producing rapidly recurring hippocampal seizures, acute decreases in prodynorphin messenger RNA were seen in the dentate gyrus and cornu Ammonis regio superior at 24 h after the last seizure. In contrast, increases in preproenkephalin messenger RNA expression were seen acutely in the dentate gyrus, with a decrease seen in the entorhinal cortex. The change in prodynorphin message expression in cornu Ammonis regio superior persisted in kindled animals that were studied after one month seizure-free period. There were no changes in preproenkephalin message in kindled animals studied after the one month seizure-free interval. No statistically significant changes were found for either prodynorphin or preproenkephalin message in the post-self-sustaining limbic status epilepticus group at one month following induced seizures. Acute changes in peptide expression may contribute to increased excitation in the dentate gyrus during induction of kindling, while the chronic change identified in cornu Ammonis regio superior may contribute directly to persistently increased excitability in this region.
 ...
PMID:Opioid peptide expression in models of chronic temporal lobe epilepsy. 760 77

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.
 ...
PMID:Activation of the c-fos gene in prodynorphin- and proenkephalin-expressing cells of nucleus tractus solitarius after seizures. 795 42

Prodynorphin mRNA and immunoreactive dynorphin A (ir-dynorphin A) levels were measured in different brain areas at various time points after amygdala kindled seizures. In the hippocampus, striatum and hypothalamus, prodynorphin mRNA levels were not significantly changed in kindled rats (killed 1 week after the last stimulus-evoked seizure), but they were significantly increased 1 h after seizures. The relative increase was the highest in the hippocampus (approximately 3-fold). In the brainstem, midbrain and cerebral cortex no changes in prodynorphin mRNA were detected in kindled rats, 1 h or 1 week after a kindled seizure. ir-Dynorphin A levels were significantly reduced in the hippocampus and in the striatum of kindled rats, as well as 5 and 60 min after kindled seizures, but they were increased back to control levels after 120 min. In the hypothalamus, ir-dynorphin A levels were significantly increased 120 min after a kindled seizure. ir-Dynorphin A levels were also significantly reduced in the brainstem and in the frontal, parietal and temporal cortex 120 min, but not 5 or 60 min, after a kindled seizure. Taken together, these data support the hypothesis that the dynorphinergic system is activated after amygdala kindled seizures, with different kinetics in different brain areas.
 ...
PMID:Early changes in prodynorphin mRNA and ir-dynorphin A levels after kindled seizures in the rat. 852 58

Levels of mRNA for c-fos and prodynorphin were studied by in situ hybridization in adjacent coronal sections taken from kindled rats 30-60 min after the last seizure. Within this time frame, expression of both genes was induced in multiple brain areas. Anatomical colocalization of the induced gene expressions was found in the hippocampus. Induction of c-fos in the dentate gyrus was bilateral and symmetrical in a subgroup of rats, ipsilateral in another subgroup and absent in a third subgroup. However, no relative increase was observed in the ipsilateral compared with the contralateral prodynorphin expression in the dentate gyrus when c-fos expression was induced ipsilaterally only. These observations suggest that, at variance with other experimental situations, Fos is not involved in the mechanisms of kindled seizure-induced activation of prodynorphin transcription in the rat forebrain.
 ...
PMID:Kindled seizure-induced c-fos and prodynorphin mRNA expressions are unrelated in the rat brain. 892 Dec 96

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.
 ...
PMID:Dextromethorphan blocks opioid peptide gene expression in the rat hippocampus induced by kainic acid. 917 61

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.
 ...
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.
 ...
PMID:Evidence for Fos involvement in the regulation of proenkephalin and prodynorphin gene expression in the rat hippocampus. 955 37

While the morphometry of classical transmitter systems has been extensively studied, relatively little quantitative information is available on the subcellular distribution of peptidergic dense core vesicles (DCVs) within axonal arbors and terminals, and how distribution patterns change in response to neural activity. This study used correlated quantitative light and electron microscopic immunohistochemistry to examine dynorphin B-like immunoreactivity (dyn B-LI) in the rat hippocampal mossy fiber pathway before and after seizures. Forty-eight hours after seizures induced by two pentylenetetrazol injections, light microscopic dyn B-LI was decreased dorsally and increased ventrally. Ultrastructural examination indicated that, in the hilus of the dentate gyrus, these alterations resulted from changes that were almost entirely restricted to the profiles of the large mossy-like terminals formed by mossy fiber collaterals (which primarily contact spines), compared to the profiles of the smaller, less-convoluted terminals found on the same collaterals (which primarily contact aspiny dendritic shafts). Dorsally, mossy terminal profile labeled DCV (/DCV) density dropped substantially, while ventrally, both mossy terminal profile perimeter and /DCV density increased. In all terminal profile examined, /DCVs also were closely associated with the plasma membrane. Following seizures, there was a reorientation of /DCVs along the inner surface of mossy terminal profile membranes, in relation to the types of profiles adjacent to the membrane: in both the dorsal and ventral hilus, significantly fewer /DCVs were observed at sites apposed to dendrites, and significantly more were observed at sites apposed to spines. Thus, after seizures, changes specific to: (1) the dorsoventral level of the hippocampal formation, (2) the type of terminal, and (3) the type of profile in apposition to the portion of the terminal membrane examined were all observed. An explanation of these complex, interdependent alterations will probably require evoking multiple interrelated mechanisms, including selective prodynorphin synthesis, transport, and release.
 ...
PMID:Morphometry of a peptidergic transmitter system: dynorphin B-like immunoreactivity in the rat hippocampal mossy fiber pathway before and after seizures. 1040 41

The opioid peptide dynorphin is thought to be implicated in specific types of seizures. In particular, complex partial seizures have been shown to cause release of dynorphin, activation of prodynorphin gene expression, and new peptide synthesis in the hippocampus. In this study, the kinetics of the seizure-induced changes in prodynorphin mRNA and ir-dynorphin A levels in the hippocampus have been compared with those induced in the temporal and frontal cortex, i.e., in other regions involved in the pathophysiology of complex partial seizures. Experiments have been run using kindling, one of the most valuable models of partial epilepsy. In the hippocampus (1) prodynorphin mRNA levels transiently increase (threefold) 1 h after kindled seizures, and return to baseline by 2 h, and (2) dynorphin A levels are slightly decreased at 1 h, but increase (twofold) at 2 h and return to baseline by 6 h. In the temporal and in the frontal cortex, a late (beginning at 2 h) and prolonged (up to 24 h) decrease in both prodynorphin mRNA and ir-dynorphin A levels have been observed. These data suggest that differential changes in dynorphin metabolism occur in different brain areas after seizures. The mechanisms and functional implications of this observation remain to be investigated.
 ...
PMID:Region-specific changes in prodynorphin mRNA and ir-dynorphin A levels after kindled seizures. 1069 Dec 94


<< Previous 1 2 3 4 Next >>