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)

By means of RIA, the contents of Leu-enkephalin, Met-enkephalin, and Beta-endorphin in CSF of 32 epileptic patients and 24 controls were determined. It was found that the mean Leu-enkephalin content in CSF of the epileptic patient group was significantly higher than that of the control group (P less than 0.01), whereas the mean contents of Met-enkephalin and Beta-endorphin in CSF showed no significant change as compared with those of the control group. The increase of Leu-enkephalin was not related to such factors as type of seizure, age of onset, length of time after the last seizure, taking of antiepileptic drugs, and abnormality in cranial CT manifestation. This suggested that endogenous opioid peptides might take part in the neurochemical mechanism of human epilepsy, and leu-enkephalin could play an important role in the development of epileptic episodes.
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PMID:[Opioid peptides in cerebrospinal fluids of epileptic patients]. 190 3

Rats were submitted to a series of 10 daily electroconvulsive shocks (ECS). A first group of animals was killed 1 day after the last seizure and a second group 30 days later. Tyrosine hydroxylase (TH) activity was measured using an in vitro assay in the nucleus caudatus, anterior cortex, amygdala, substantia nigra, ventral tegmental area, and locus ceruleus. The mRNA corresponding to this enzyme (TH-mRNA) was evaluated using a cDNA probe at the cellular level in the ventral tegmental area, substantia nigra, and locus ceruleus. Met-enkephalin (MET)-immunoreactivity and the mRNA coding for the preproenkephalin (PPE-mRNA) were assayed in striatum and the central nucleus of the amygdala. The day after the last ECS an increase of TH activity was observed in the ventral tegmental area, locus ceruleus, and substantia nigra in parallel with a similar increase in the amygdala and striatum; in the anterior cortex TH activity remained unchanged. TH-mRNA was increased in the locus ceruleus, evidencing the presence in this structure of a genomic activation. The amounts of MET and PPE-mRNA were unaffected in the striatum but increased in the amygdala. Thirty days after the last ECS we observed a decrease of TH activity in the amygdala and of TH-mRNA amount in the ventral tegmental area. In the locus ceruleus TH-mRNA remained higher in treated animals than in controls whereas TH activity returned to control levels. These results demonstrate that a series of ECS induces an initial increase of the activity of mesoamygdaloid catecholaminergic neurons followed by a sustained decrease through alterations of TH gene expression which could mediate the clinical effect of the treatment.
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PMID:Short- and long-term alterations of gene expression in limbic structures by repeated electroconvulsive-induced seizures. 196 90

Recent studies have demonstrated that the regulation of neuropeptide expression in forebrain neurons is responsive to external influences including changes in physiological activity. This has been demonstrated most clearly in studies of hippocampus where the synthesis and resting levels of several neuropeptides, localized within well-characterized components of hippocampal circuitry, have been shown to be selectively influenced by seizure activity. In studies described here, we examined the influence of recurrent limbic seizures on the expression of enkephalin, dynorphin, cholecystokinin, and neuropeptide Y (NPY) in rat and mouse hippocampus using immunohistochemical, in situ hybridization and blot hybridization techniques. The data demonstrate that seizures differentially influence the expression of each peptide as a part of a broader cascade of changes in genomic expression within individual hippocampal neurons. In particular, seizures increase preproenkephalin mRNA and enkephalin peptide but decrease dynorphin peptide in the dentate gyrus granule cell/mossy fiber system. Seizure-induced decreases in the concentration of preprodynorphin mRNA in the granule cells have been reported by others. Immunoreactivity for CCK, which is codistributed with the opioid peptides in the mossy fiber system of mouse, is also dramatically reduced in the granule cell axons by seizure. Recurrent seizures induce two temporally distinct changes in NPY expression in hippocampus. First, there is an increase in hybridization to preproNPY mRNA within scattered, probable local circuit neurons in all subfields. This is followed by the seemingly novel appearance of preproNPY mRNA within the dentate gyrus granule cells and pyramidal cells of field CA1. Clues about mechanisms of neuropeptide regulation have come from observations of other, more rapid, transcriptional events induced by seizure. Most notably, our results and those of others demonstrate that seizures increase the expression of messenger RNAs from immediate-early genes (c-fos, c-jun, and NGFI-A) which encode proteins that may mediate neuropeptide gene regulation. In addition, mRNA for nerve growth factor is dramatically increased in the dentate gyrus granule cells by seizure; increased production of this trophic factor might mediate the more delayed changes in genomic expression and growth responses observed to occur in hippocampus and other forebrain areas following seizure activity.
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PMID:Seizures, neuropeptide regulation, and mRNA expression in the hippocampus. 220 4

The specificity of the hypoglycemic response to the intrathecal (i.t.) administration of the naturally occurring (-)-enantiomer of morphine previously reported from our laboratory was studied in mice. (+)-Morphine HBr (50 micrograms) caused a behavioral syndrome (scratching, biting, seizures) comparable to that produced by (-)-morphine sulfate (50 micrograms), but did not cause hypoglycemia. Many opioids, at a dose of 50 micrograms i.t. in nonfasted mice, showed either a saline-like hyperglycemic response or no significant effect on blood glucose. (+)-Morphine, ketocyclazocine, U-50,488, (-)- and (+)-N-allyl-normetazocine, beta-endorphin, (-)- and (+)-naloxone and naltrexone caused hyperglycemia. Significant changes from basal blood glucose were not produced by [D-Pen2, L-Pen5]-enkephalin, [D-Ser2]-Leu-enkephalin-Thr or sufentanil in 50-micrograms doses, or by codeine (300 micrograms), levorphanol (400 micrograms) or methadone (200-400 micrograms). Agonists which produced both hypoglycemic and behavioral effects were, in order of decreasing potency, hydromorphone greater than normorphine greater than morphine greater than 6-acetylmorphine greater than oxymorphone much greater than heroin. Morphine-induced hypoglycemia was partially antagonized by the i.t. coadministration of naloxone methobromide (10 micrograms). Fasting for 24 hr increased the sensitivity to hypoglycemic and lethal effects of morphine. D-Ala2-N-Me-Phe4-Gly5-ol]-enkephalin (5-50 micrograms i.t.) tended to decrease blood glucose in both nonfasted and fasted mice, but these effects were moderate and appeared to be unrelated to dose.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypoglycemia induced by intrathecal opioids in mice: stereospecificity, drug specificity and effect of fasting. 235 29

The biochemical and pharmacological properties of an endogenous anticonvulsant substance(s) found in rat cerebrospinal fluid (CSF) following seizures are described. CSF taken from donor rats following a single maximal electroshock (MES) seizure caused significant elevations in seizure thresholds in naive recipient rats when intracerebroventricularly injected 15 min prior to exposure to the volatile convulsant flurothyl. Anticonvulsant activity was antagonized by pre-injection in recipients of high doses of naloxone or the selective delta-opioid receptor antagonist ICI 174,864. The anticonvulsant activity was also lost when the CSF was exposed to heat (90 degrees C) or immobilized trypsin. Although unaffected by the peptidase inhibitors thiorphan and bestatin, the anticonvulsant activity was significantly potentiated by a combination of aprotinin and bacitracin. Ultrafiltration of CSF revealed that the anticonvulsant activity passed through membranes with a 10,000 molecular weight cut-off, but was retained by membranes with a 5000 molecular weight cut-off. CSF removed from rats following MES had significantly increased concentrations of beta-endorphin-like, but not dynorphin A, Leu- or Met-enkephalin-like immunoreactivities relative to CSF from sham-treated rats. However, significant increases in Met-enkephalin-like immunoreactivity were measured following exposure of the CSF to the proteolytic enzymes trypsin and carboxypeptidase B, suggesting the seizure-induced presence of a higher molecular weight form of Met-enkephalin not recognized immunologically prior to enzyme exposure. These data reconfirm the anticonvulsant actions of postseizure CSF, and indicate that these effects require mediation through delta-opioid receptors in the recipient rat. These data additionally argue against these effects being mediated by Met-enkephalin, Leu-enkephalin or dynorphin A in the CSF, and suggest instead that anticonvulsant effects are attributable to a heat- and trypsin-sensitive opioid peptide(s) with a molecular weight approximately in the range of 5000-10,000 Da.
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PMID:Characterization of opioid peptide-like anticonvulsant activity in rat cerebrospinal fluid. 245 10

Using amygdaloid kindling in chronic rats, we were able to observe behavioral, electrographic and IR-Met- and IR-Leu-enkephalin changes throughout the progress of different stages of convulsive activity. Rats presenting the initial stages of kindling, rats presenting the first generalized motor seizure, and rats with at least 10 generalized seizures were sacrificed 24 h after the last stimulus; also rats with at least 10 generalized seizures but sacrificed 21 days after the last seizure were compared with control and sham-operated groups of rats. The IR-Met and IR-Leu enkephalin concentrations in each group were measured in the striatum, amygdala, hypothalamus, medulla oblongata (including pons), hippocampus, mid-brain, spinal cord and cerebral cortex. A progressive increase in IR-Leu-enkephalin in amygdala and hippocampus was observed over the course of kindling. These increases remained until 21 days after rats were fully kindled (at least 10 generalized seizures). We observed increased and decreased concentration of each peptide in different regions. We discussed the regional and the differential effects of each peptide. The increased concentrations in limbic structures were associated with the amygdaloid increased excitability through the kindling process. We suggest that the decreases in concentrations are related with structures involved in the output behavior manifestations produced by kindling stimulation.
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PMID:Regional brain IR-Met-, IR-Leu-enkephalin concentrations during progress and full electrical amygdaloid kindling. 272 Mar 96

Male Fischer-344 rats were given a single intrastriatal injection of kainic acid (KA; 1 microgram/rat), which caused recurrent motor seizures lasting 3-6 hr. During the convulsive period, native Met5-enkephalin-like (ME-LI) and dynorphin A (1-8)-like (DYN-LI) immunoreactivities in hippocampus decreased by 31 and 63%, respectively. By 24 hr after dosing, the hippocampal opioid peptides had returned to control levels, and by 48 hr ME-LI had increased 270% and DYN-LI 150%. Immunocytochemical analysis revealed that ME-LI and Leu5-enkephalin-like (LE-LI) immunostaining in the mossy fibers of dentate granule cells and the perforant-temporoammonic pathway had decreased visibly by 6 hr and had increased markedly by 48 hr following KA. A visible decrease in DYN-LI in mossy fiber axons within 6 hr was followed by a substantial increase by 48 hr. To determine whether the increases in hippocampal ME-LI reflected changes in ME biosynthesis, levels of mRNA coding for preproenkephalin (mRNAenk) and cryptic ME-LI cleaved by enzyme digestion from preproenkephalin were measured. Following the convulsive period (6 hr), mRNAenk was 400% of control, and by 24 hr, cryptic ME-LI was 300% of control. Increases in native and cryptic ME-LI and in mRNAenk were also noted in entorhinal cortex, but not in hypothalamus or uninjected striatum. Our data suggest that KA-induced seizures cause an increase in ME release, followed by a compensatory increase in ME biosynthesis in the hippocampus and entorhinal cortex.
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PMID:Kainic acid alters the metabolism of Met5-enkephalin and the level of dynorphin A in the rat hippocampus. 287 67

Kainic acid (KA), an excitatory neurotoxin, was used as a tool to study the metabolism of hippocampal opioid peptides and their functional role in the expression of wet-dog shakes (WDS). A single intracerebral injection of KA (1 microgram/rat) caused recurrent motor seizures lasting 3-6 h. During the convulsive period, native Met5-enkephalin-like (ME-LI) and dynorphin A(1-8)-like (DYN-LI) immunoreactivities in hippocampus decreased by 31 and 63%, respectively. By 24 h after dosing, the hippocampal opioid peptides had returned to control levels, and by 48 h ME-LI had increased 270% and DYN-LI 150%. Immunocytochemical analysis revealed that ME-LI and Leu5-enkephalin-like (LE-LI) immunostaining in the mossy fibers of dentate granule cells and the perforant-temporoammonic pathway had decreased visibly by 6 h and had increased markedly by 48 h following KA. A visible decrease in DYN-LI in mossy fiber axons within 6 h was followed by a substantial increase at 48 h. To determine whether the increases in hippocampal ME-LI reflected changes in ME biosynthesis, levels of mRNA coding for preproenkephalin (mRNAenk) and cryptic ME-LI cleaved by enzyme digestion from preproenkephalin were measured. Following the convulsive period (6 h), mRNAenk was 400% of control, and by 24 h, cryptic ME-LI was 300% of control. Increases in native and cryptic ME-LI and in mRNAenk were also noted in entorhinal cortex, but not in hypothalamus or uninjected striatum. Our data suggest that KA-induced seizures cause an increase in ME release, followed by a compensatory increase in ME biosynthesis in the hippocampus and entorhinal cortex. Several lines of evidence from this study have suggested that hippocampal enkephalins are intimately related to KA-elicited WDS. The shaking behavior was attenuated by pretreatment with naloxone or antisera against [Met5]-enkephalin. We also observed that KA-induced WDS can be mimicked by intrahippocampal injection of enkephalin-related peptides. Furthermore, this study demonstrated that intact dentate granule cells are essential for KA- and enkephalin-induced WDS, since a colchicine injection into the ventral hippocampus, which selectively destroys granule cells, abolished this behavior.
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PMID:Kainic acid as a tool to study the regulation and function of opioid peptides in the hippocampus. 289 Feb 24

Bilateral, recurrent seizures were induced in adult male rats by a unilateral, electrolytic lesion of the dentate gyrus hilus. This treatment led to a bilateral depletion of enkephalin-like immunoreactivity in the hippocampal mossy fibers by 12 hours (h) post-lesion, a rebound above normal levels by 24 h, a further rise by 4 days than a fall to control values by 10 days post-lesion. The mRNA for preproenkephalin was elevated in the granule cells by 3h post-lesion, reached a maximal 24-fold rise by 30 h then fell again to control values by 4-10 days post-lesion.
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PMID:Increased enkephalin gene expression in the hippocampus following seizures. 312 57

The amounts of the mRNAs for the neuropeptide precursor proteins preproenkephalin, preprocholecystokinin and preproneuropeptide Y were measured in the entorhinal cortex of normal rats and rats that had experienced recurrent limbic seizures induced by a small contralateral lesion of the dentate gyrus hilus. Additionally, the amount of mRNAs for preproenkephalin as well as for the cellular proto-oncogenes c-myc, c-fos and c-H-ras, which are thought to be mediators of intracellular signal transduction, was determined in hippocampus in these same animals. It was determined that the hilus lesion led to a dramatic (18-fold) increase in the content of preproenkephalin mRNA in the entorhinal cortex whereas only a modest increase in preproneuropeptide Y mRNA content and no change in preprocholecystokinin mRNA was detected in this same brain region. In hippocampus a large and very rapid increase in c-fos mRNA was observed to precede the previously reported increase in preproenkephalin mRNA following hilus lesion-induced seizures. Like the increase in opioid peptide mRNA, the increase in c-fos mRNA began early in the period of seizure activity and could be blunted by maintaining the animals under anesthesia with the anticonvulsant sodium pentobarbital. Messenger RNA for c-H-ras was not altered at any time following the lesion and c-myc mRNA was not reliably detected in either control or hilus lesioned rats. These data demonstrate that neuropeptide genes within the entorhinal cortex and proto-oncogenes within the hippocampus are differentially regulated by seizure activity and suggest that the c-fos proto-oncogene may be involved in events which mediate the physiological regulation of enkephalin gene expression.
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PMID:Differential regulation of neuropeptide and proto-oncogene mRNA content in the hippocampus following recurrent seizures. 342 45


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