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 changes of opioid peptide reactivity in seizure activity have been well studied in animals. Increased enkephalin and dynorphin immunoreactivity in the hippocampi of animals are interpreted as the result of seizure induced mossy fibre sprouting. We studied the hippocampi of six patients with a history of long-standing grand mal seizures and six age-matched control patients with no history of epilepsy or neurologic disease, using frozen sections which were immunostained with antibodies against Leu-enkephalin and Met-enkephalin. The staining intensity in the CA3, CA4 and internal molecular layer of the dentate fascia in each case was quantified using optical densitometry image analysis. The CA3 and CA4 of the epileptic hippocampi showed highly significant increase in Leu-enkephalin-like immunoreactivity compared to the controls (P < 0.005) while the inner molecular layer showed only significant increase (P < 0.05). Met-Enkephalin-like immunoreactivity was only significantly increased in CA4 of the epileptic hippocampi (P < 0.05).
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PMID:Increase in enkephalin-like immunoreactivity in hippocampi of adults with generalized epilepsy. 795 7

The ontogeny of kainate induction of AP-1 mRNAs, proteins, and DNA binding activities was examined in the rat hippocampus. In addition, kainate induction of preproenkephalin and preprodynorphin mRNAs was examined; these genes have been shown to be induced by kainate and have been suggested to be targets of AP-1 regulation in adult rat hippocampus. Despite producing seizures at postnatal day (P) 7, kainate failed to induce AP-1 or opiate gene expression and did not increase AP-1 DNA binding activity at this age. Basal levels of AP-1 and opiate mRNAs were low in P7 hippocampus. Basal levels of c-jun protein and AP-1 DNA binding activity were elevated in the P7 hippocampus, to values greater than induced levels in adult hippocampus. Furthermore, AP-1 DNA binding in P7 hippocampal nuclear extract was unaffected by antibodies against fos-related antigens, in contrast to hippocampal extracts from the older rats examined. At P14, induction of AP-1 and preproenkephalin (but not preprodynorphin) mRNAs was observed with kainate treatment, but the time course for inductions was delayed relative to kainate inductions in the adult hippocampus. At P21, responses to kainate were similar to the adult response. Unlike in adult hippocampus, seizure activity caused by kainate treatment does not increase the transcription factor and opioid peptide gene expression in the hippocampi of P7 rats.
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PMID:Ontogeny of kainate-induced gene expression in rat hippocampus. 829 5

In the rat hippocampus, jun, c-fos, and fos-related antigen immunoreactivity, AP-1 DNA binding, and opioid peptide gene expression were examined after kainate treatment to determine whether the induction and DNA binding of AP-1 transcription factors are correlated with the expression of the opioid peptide genes. One and one-half hours after kainate administration, fos-related antigen and jun immunoreactivity and AP-1 DNA binding were induced; maximal elevation was observed after 4.5 h. Transcription factor expression and DNA binding increased in a dose-dependent manner. Preprodynorphin and preproenkephalin mRNA induction was also dose dependent. The anticonvulsants, pentobarbital and diazepam, effectively blocked electroencephalographic seizure activity caused by kainate treatment, whereas valproic acid was approximately 50% effective. Opioid peptide gene expression, fos-related antigen and jun immunoreactivity, and AP-1 DNA binding all reflected similar reductions after anticonvulsant treatment. Therefore, expression and DNA binding activity of the AP-1 transcription factors are correlated with opioid peptide gene expression in the rat hippocampus.
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PMID:Kainate-induced changes in opioid peptide genes and AP-1 protein expression in the rat hippocampus. 841 41

Opioid peptide release in the hippocampus was shown to be increased immediately following amygdala kindling stimulation in freely moving rats using microdialysis combined with a universal opioid peptide radioimmunoassay (RIA). Extracellular opioid peptide levels were elevated (55% above basal levels) within the first 10 min after electrical stimulation-induced partial seizures in previously nonkindled animals. Fully kindled rats showed lower extracellular opioid peptide levels (40% reduction) during the interictal period [16 +/- 2.1 days (mean +/- SEM) after the last stage V seizure], in comparison with values obtained from the sham-kindled group under basal conditions. However, opioid peptide release in fully kindled rats increased above 152% of interictal levels within the first 20 min after onset of fully kindled seizures, attaining peak levels equal to that of the partial kindled group and returning to prestimulation conditions 40-60 min following the ictal events. The majority of the immunoreactive material recovered from the hippocampus within the first 20 min following partial and generalized kindled seizures coeluted with dynorphin-A (1-6), dynorphin-A (1-8), and Leu-enkephalin by HPLC/RIA analysis. It is proposed that the enhanced opioid peptide release in hippocampus induced by amygdala kindling stimulation might be associated with either enhanced excitability or seizure suppression as seizure susceptibility fluctuates. The reduced interictal opioid peptide levels may also underlie some interictal behavioral disturbances.
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PMID:Amygdala kindling modifies extracellular opioid peptide content in rat hippocampus measured by microdialysis. 900 48

Kainic acid-induced status epilepticus results in delayed degeneration of CA3 hippocampal neurons in the mature but not immature rat hippocampus. In adult rats, the putative opioid precursor, preproenkephalin (PPE) mRNA increases in the dentate gyrus (DG), a region resistant to damage, following continuous limbic seizures. To explore why the immature brain is resistant to seizure-induced damage, the regional distribution of PPE mRNA expression and 45Ca2+ accumulation were compared in postnatal day 14 (P14) pup, and adult hippocampus at 5-6 h after kainate-induced status epilepticus. Inverted patterns of PPE expression and Ca2+ uptake were observed at the two ages. In P14 pups, PPE mRNA expression increased in DG and escalated in CA3, regions where 45Ca2+ accumulations were absent. In adult rats, PPE mRNA expression increased only in DG; 45Ca2+ labeling was predominant in CA3a,c and absent in DG. Pronounced increases in enkephalin neuropeptide synthesis in immature CA3 neurons may reduce glutamate release presynaptically and also prevent voltage-gated Ca2+ uptake into these neurons despite recurrent seizure activity. Opioid-mediated inhibition may provide an explanation for the resistance of the immature CA3 region to seizure-induced damage.
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PMID:Developmental switch in phenotypic expression of preproenkephalin mRNA and 45Ca2+ accumulation following kainate-induced status epilepticus. 926 4

Inbred animal strains provide an opportunity to study genetic factors in alcoholism in the absence of environmental factors. Although the concentration of methionine enkephalin (Met-enkephalin) in whole brain has been implicated in the consumption of ethanol, it has not been studied in the brains of alcohol withdrawal seizure-prone (WSP) and withdrawal seizure-resistant (WSR) mice. We compared these concentrations with the levels of preproenkephalin (PPE) mRNA and with the activity of peptide transport system-1 (PTS-1), a brain-to-blood transport system for Met-enkephalin that is affected by ethanol. The concentrations of Met-enkephalin were significantly greater in WSP mice than in WSR mice, whereas synthesis of Met-enkephalin, as reflected by PPE mRNA levels, and transport out of the brain by PTS-1 was not different. These results support a direct link between elevated concentrations of Met-enkephalin in whole brain and proneness to withdrawal-induced seizures. We suggest that the inverse relationship between the consumption of ethanol and proneness to seizures in inbred mice can be explained through their opposite relationships to Met-enkephalin.
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PMID:Enkephalin, PPE mRNA, and PTS-1 in alcohol withdrawal seizure-prone and -resistant mice. 942 34

Met-enkephalin release is increased from amygdala and striatum 1 and 15 days after pharmacological kindling with pentylenetetrazol, following potassium-induced depolarization in vitro via a Ca2+ dependent mechanism. Leu-enkephalin release was only enhanced in amygdala and striatum 1 day after the last seizure. IR-Met-enkephalin amygdala tissue content enhanced 1 and 15 days after seizure. In striatum, we found an IR-Met-enkephalin decrease 35 days after the last stimulus. IR-Leu-enkephalin amygdala tissue content enhanced 1 day after the last seizure, and no significant increases were found in striatum 1, 15 and 35 days after the last seizure. In this paper, we show that opioid peptides release is differentially enhanced in rat brain for several days after the last seizure, thus suggesting that opioid peptides may have a protective action against seizure activity.
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PMID:Long-term pharmacological kindling increases in vitro release of IR-Met and IR-Leu-enkephalin from amygdala. 977 7

In a model of self-sustaining status epilepticus induced in rats by 30 min intermittent stimulation of the perforant path through chronically implanted electrodes, a decrease in dynorphin-like immunoreactivity in the dentate gyrus and CA3 was observed 3 h and 24 h after the induction of status epilepticus. Enkephalin-like immunoreactivity decreased 3 h but not 24 h after perforant path stimulation. Injection into the hilus of the dentate gyrus 10 min prior to stimulation of the kappa-receptor agonist dynorphin-A(1-13), the delta-receptor antagonists ICI-174864 and naltrindole, as well as i.p. injection of naloxone prevented the development of status epilepticus. Perihilar administration of the delta-agonist [D-Ser2]Leu-enkephalin-Thr6 or the kappa-antagonist nor-Binaltorphimine, but not of the mu-agonist [D-Ala2,N-Me-Phe4,Gly-ol5]-Enkephalin, facilitated the establishment of self-sustaining status epilepticus. Injection into the hilus of dynorphin-A(1-13) after the end of perforant path stimulation, stopped established status epilepticus, while administration of naloxone, naltrindole and ICI-174864 were ineffective. We conclude that kappa-opioids in the hippocampus counteract initiation and maintenance of status epilepticus, while delta-opioids promote initiation, but not maintenance of seizure activity. These data are important for the understanding the mechanisms which underlie initiation and maintenance of status epilepticus and for the development of new approaches for its effective management.
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PMID:Opioid peptide pharmacology and immunocytochemistry in an animal model of self-sustaining status epilepticus. 1005 Dec 26

Methionine enkephalin (Met-enkephalin) functions as an endogenous anticonvulsant. Peptide transport system-1 (PTS-1) is an important regulator of Met-enkephalin levels in brain and transports the peptide from brain to blood. In outbred mice, alcohol dependence is associated with decreased PTS-1 activity and increased levels of Met-enkephalin. In contrast, alcohol withdrawal is associated with recovery of PTS-1 activity, decreased levels of Met-enkephalin, and seizures. In this study, we examined the PTS-1/Met-enkephalin system in two replicates of withdrawal seizure-resistant (WSR) and withdrawal seizure-prone (WSP) mouse lines. We measured levels of preproenkephalin (PPE) mRNA and Met-enkephalin peptide in brain and the activity of PTS-1 during alcohol-naive, -dependent, and -withdrawal states. In alcohol-naive animals, Met-enkephalin levels were higher in WSP than in WSR mice. In alcohol-withdrawal animals, Met-enkephalin levels remained elevated in WSP mice, whereas they increased in WSR mice. Peptide levels were unrelated to levels of PPE mRNA or activity of PTS-1. Factorial analysis showed that proneness to seizures was genetically linked to Met-enkephalin levels in alcohol-naive, -dependent, and -withdrawing mice but not to mRNA levels or PTS-1 activity. Overall, these results may be explained by resistance to enkephalin in WSP mice and suggest that the dysregulation of the PTS-1/Met-enkephalin system contributes to susceptibility to seizures in WSP mice.
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PMID:Withdrawal from alcohol in withdrawal seizure-prone and -resistant mice: evidence for enkephalin resistance. 1132 89

In this study, the glutamate receptor agonist, NMDA, was used to induce epileptic seizures in order to compare the expression of the immediate early gene (IEG) products, Fos and Fos-related antigens (Fras), with the opioid peptides, dynorphin (DYN) and leu(5)-enkephalin (LE), in the rat hippocampus. Fos-ir and Fra-ir were observed in the dentate granule cells and nonpyramidal cells within the hippocampal formation at 1 h, and in all hippocampal cells and fields, 3 h following injection of NMDA into the ventral hippocampus. A detailed time-course analysis revealed a differential expression of Fos-ir and Fra-ir. In adjacent sections, a substantial decrease in DYN-ir and LE-ir in the mossy fibers occurred 1, 3, and 6 h after NMDA which was followed by a normalization or an elevation of the opioid peptides at later time points. Quantitative in situ hybridization histochemistry revealed that the hybridization signal representing c-fos mRNA was induced rapidly and transiently in hippocampal neurons. An increase in preproenkephalin (PPE) mRNA in the dentate granule cells was observed 1, 3, and 6 h after NMDA, with a peak at 6 h. Twenty-four and 48 h after NMDA, hybridization signals for PPE and preprodynorphin (PPD) were barely detectable. At 72 h, the level of PPD mRNA was not significantly different from control values. There is a different time course of expression for the Fos and Fra family of genes after in vivo NMDA. The significance of the results is discussed with regard to IEG regulation of opioid peptide gene expression.
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PMID:Intrahippocampal NMDA Administration Alters Fos, Fos-Related Antigens, and Opioid Peptide Immunoreactivity and mRNA in Rats. 1991 39


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