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)

Pentylenetetrazole (PTZ) evoked seizures, known to be dependent on stimulation of excitatory amino acids (EAA) receptors, serve as a useful model to study genomic responses to increased brain activity. It is believed that these responses form the basis for long term modifications in neuronal functions. Formation of the AP-1 transcription factor genes and proteins in hippocampal cells is the best known example of a genomic response to PTZ seizures and to an activation of the EAA receptors. In the studies reported herein electrophoretic mobility shift assay (EMSA) was employed to investigate levels of AP-1 DNA binding activity in various regions of the rat brain following PTZ seizures and these levels were compared to the cyclic AMP responsive element (CRE) DNA binding activity. A dramatic increase of the AP-1 DNA binding activity was observed in the hippocampus and in sensory and limbic cortices, and to much lesser extent in the cerebellum. The EMSA supershift method provided an evidence that Jun B and c-Fos and probably Fos B are major components of AP-1 at 2 h after the seizures. In none of the structure investigated, clear modulation of CRE DNA binding activity was noted. These data are discussed in the context of CRE and AP-1 DNA binding crossreactivity.
 ...
PMID:AP-1 and CRE DNA binding activities in rat brain following pentylenetetrazole induced seizures. 803 18

Chemically provoked seizures have proved to serve as useful model to investigate long term neuronal responses collectively termed as neuronal plasticity. In particular, rapid, transient activation of immediate early gene expression induced by such chemoconvulsants like pentylenetetrazole (PTZ) and kainic acid (KA) drew a great attention. These genes code for transcription factors, known to influence gene expression, and therefore able to orchestrate genomic responses to extracellular stimuli. In our studies reviewed herein and reported in detail elsewhere, we have investigated PTZ- and KA-dependent activation of a functional feature of transcription factors i.e. their DNA-binding activity. We have found that only AP-1 DNA-binding activity was elevated in the rat hippocampus, entorhinal and sensory cortices 2-6 h after the PTZ administration, and only in the hippocampus and entorhinal cortex at similar times following KA injection. The AP-1 response to PTZ was strikingly enhanced in aged (18-24 months old) animals when compared to young (3 months old) ones. KA, apart from this early phase of AP-1 DNA-binding activity increase, evoked also the late one (reaching a peak value at 72 h). The protein composition of the latter differed from the former mostly by substitution of Jun B with Jun D protein and lack of c-Fos. Because the KA treatment leads not only to the seizures but to apoptosis (programmed cell death) as well, our results indicate that various AP-1 complexes may be involved in both of these phenomenon.
 ...
PMID:Seizures-evoked activation of transcription factors. 805 14

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.
 ...
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.
 ...
PMID:Kainate-induced changes in opioid peptide genes and AP-1 protein expression in the rat hippocampus. 841 41

The influence of glucocorticoids on the transcription factor NFkB was investigated by using the gel mobility shift assay with nuclear extracts prepared from rat cerebral cortex and hippocampus after a variety of in vivo treatments. Following stimulation with each of three treatments, kainate, pilocarpine, or lithium plus pilocarpine-induced seizures, NFkB DNA binding activity was significantly greater in the cortex and hippocampus from adrenalectomized than from adrenal-intact rats. These results indicate that in rat brain glucocorticoids inhibit NFkB activity in addition to the previously reported inhibition of the transcription factor AP-1 (activator protein 1). Impairment of stimulus-induced transcription factor activity may contribute to the deleterious effects of prolonged elevations of glucocorticoids on neuronal function.
 ...
PMID:Inhibition of NFkB DNA binding activity by glucocorticoids in rat brain. 857 92

The potential influence of a circadian rhythm and its modulation by lithium on the stimulation of AP-1 DNA binding activity by the cholinergic agonist pilocarpine was investigated in rat cerebral cortex. Stimulation of AP-1 binding after pilocarpine (30 mg/kg) was evident within 1 h and was maximally stimulated by 200% at 2 h. Pilocarpine-stimulated AP-1 binding exhibited a circadian rhythm in AP-1 binding measured at 0800, 1200, and 1600 hours, 2 h after pilocarpine. Pilocarpine-stimulated AP-1 binding at 0800 hours was approximately twice the level measured at 1600 hours. After acute lithium treatment, pilocarpine administration induced generalized seizures after about 20 min and stimulated AP-1 binding which increased continuously for 4.5 h, at which time the stimulation was 900% above control. A circadian variation was apparent in AP-1 binding stimulated by acute lithium plus pilocarpine, with stimulation at 0800 hours being 1.5 times that at 1600 hours. After chronic lithium and pilocarpine, which also produced seizures, there was no circadian variation in pilocarpine-stimulated AP-1 binding. Thus pilocarpine-induced AP-1 binding in rat cerebral cortex was influenced by a circadian rhythm, but this was abolished by chronic lithium administration.
 ...
PMID:Circadian variation in rat brain AP-1 DNA binding activity after cholinergic stimulation: modulation by lithium. 865 34

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.
 ...
PMID:Neuronal activity increases the phosphorylation of the transcription factor cAMP response element-binding protein (CREB) in rat hippocampus and cortex. 866 77

We examined the involvement of the GABAB receptor and the coordinated induction of nuclear transcriptional factors in experimental generalized absence seizures induced by gamma-butyrolactone (GBL) in mice. Although administration of GBL 50 mg/kg did not show any effects on behavior or ECoG pattern, higher doses of GBL (70 and 100 mg/kg, i.p.) induced behavioral changes associated with 3-6-Hz spike and wave discharges in the mice. CGP 35348, a GABAB receptor antagonist, suppressed both the GBL-induced absence seizures and the spike and wave discharges. The antiepileptic effects of CGP 35348 (200 mg/kg, i.p.) were stronger than those of ethosuximide (200 mg/kg, i.p.). Sodium valproate (100 mg/kg, i.p.) attenuated the early phase but not the late phase of the GBL-induced absence seizures. Gel-mobility assay demonstrated that administration of an effective dose of GBL for eliciting spike and wave discharges dose-dependently increased nuclear cyclic AMP-responsive element (CRE)- and activator protein 1 (AP-1) DNA-binding activities in mouse whole brain. The increases in nuclear CRE- and AP-1 DNA-binding were antagonized by CGP 35348 in a dose-dependent fashion. In addition, GABAB receptor binding assay revealed that GBL or antiepileptic drugs did not displace [3H]baclofen binding in cerebral cortical membranes. In contrast, gamma-hydroxybutyrate (GHB), an active metabolite of GBL, inhibited [3H]baclofen binding in a concentration-dependent manner. These results suggest that GABAB receptor-mediated synaptic responses are involved in GBL-induced generalized absence seizures and that the increases in nuclear CRE- and AP-1 DNA-binding activities are correlated with the GBL-induced generalized absence seizures.
 ...
PMID:gamma-Butyrolactone-induced absence-like seizures increase nuclear CRE- and AP-1 DNA-binding activities in mouse brain. 868 96

Several studies have shown that dextromethorphan (DM) has both anticonvulsant and proconvulsant effects depending on the animal model. In this study, we examined the effects of DM on three parameters associated with kainic acid (KA)-induced seizures: cell loss in the hippocampus, increased AP-1 DNA binding activity and increased c-Jun and fos-related antigen (FRA) expression. KA administration (8 mg/kg, ip) produced robust behavioral convulsions lasting 4-6 hr. Pretreatment with DM (12.5-75 mg/kg, po) 15 min before KA injections reduced the seizures as well as mortality in a dose-dependent manner. Histological studies revealed a severe loss of cells in the CA1 and CA3 fields of the hippocampus in KA-treated rats. DM pretreatment also reduced this cell loss in a dose-dependent fashion. Biochemical studies showed that DM pretreatment also attenuated the KA-induced increase of AP-1 binding activity and c-Jun/FRA expression in the hippocampus. These results indicate that DM is an effective antagonist of KA.
 ...
PMID:The effects of dextromethorphan on kainic acid-induced seizures in the rat. 885 34

The expression of the proteins (C-FOS and C-JUN) encoded by the immediate early genes c-fos and c-jun was investigated in the brains of rats undergoing ethanol withdrawal. Both proteins were induced in the cerebral cortex, the piriform cortex, the olfactory bulb, the inferior colliculus, the granular cell layer of the cerebellum and in the brain stem, but only C-JUN was induced in the hippocampus of animals undergoing withdrawal without overt seizures. C-FOS was detected in the hippocampus only in animals with overt seizures. Maximal C-FOS expression occurred 15 hr after withdrawal while C-JUN was maximal at 24 hr. Gel-shift assays indicated the formation of AP-1 binding factors in nuclear extracts of the cerebral cortex, hippocampus and cerebellum 15 and 17 hr after withdrawal. These data reveal a complex pattern of immediate early gene expression during ethanol withdrawal, which may be associated with changes in neuronal plasticity underlying phenomena such as withdrawal kindling.
 ...
PMID:Gene expression during ethanol withdrawal. 897 22


<< Previous 1 2 3 4 5 6 Next >>