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)

Specific [3H]MK801 binding to rat brain NMDA receptors after the administration of the convulsant drug 3-mercaptopropionic acid (MP) and the adenosine analogue cyclopentyladenosine (CPA) was studied by means of a quantitative autoradiographic method. MP administration (150 mg/kg, i.p.) caused significant decreases in [3H]MK801 binding in several hippocampus subareas and layers, mainly in CA1 and CA3 at seizure (11-27%) and postseizure (8-16%) and in cerebral occipital cortex at seizure (18-22%). In nucleus accumbens, a rise was observed at postseizure (44%) and a tendency to increase at seizure (24%). CPA (2mg/kg, i.p.) decreased ligand binding in hippocampus (CAI, CA2, CA3) (17-22%) and in occipital cerebral cortex (18-24%). When CPA was administered 30 minutes before MP (which delayed seizure onset) and rats were sacrificed at seizure, decreases in [3H]MK801 binding in several layers of CA1 and CA3 of hippocampus (11-27%) and in CA1, CA2, CA3 (24-35%) after CPA+MP postseizure, and an increase in CA2 after CPA and CPA+MP postseizure (20-34%), were observed. A drop was found in the occipital subarea (18-24%) after CPA and in the frontal and occipital subarea after CPA+MP postseizure (24-34%) while no changes were observed in any treatment involving the other cerebral cortex regions, thalamic nuclei, caudate putamen and olfactory tubercle. These results show that [3H]MK801 binding changes according to drug treatment and the area being studied, thus indicating a different role in seizure activity.
 ...
PMID:Modification of [3H]MK801 binding to rat brain NMDA receptors after the administration of a convulsant drug and an adenosine analogue: a quantitative autoradiographic study. 980 90

This study determined whether hippocampal kainate (KA) receptor mRNA levels were increased or decreased in temporal lobe epilepsy patients compared with nonseizure autopsies. Hippocampal sclerosis (HS; n = 17), nonsclerosis (non-HS; n = 11), and autopsy hippocampi (n = 9) were studied for KA1-2 and GluR5-7 mRNA levels using semiquantitative in situ hybridization techniques, along with neuron densities. Compared with autopsy hippocampi, HS and non-HS cases showed decreased GluR5 and GluR6 hybridization densities per CA2 and/or CA3 pyramid. Furthermore, HS patients demonstrated increased KA2 and GluR5 hybridization densities per granule cell compared with autopsy hippocampi. These findings indicate that chronic temporal lobe seizures were associated with differential changes in hippocampal KA1-2 and GluR5-7 hybridization densities that vary by subfield and pathology group. In temporal lobe epilepsy patients, these results support the hypothesis that pyramidal cell GluR5 and GluR6 mRNA levels are decreased as a consequence of seizures, and in HS patients granule cell KA2 and GluR5 mRNA levels are increased in association with aberrant fascia dentata mossy fiber sprouting and/or hippocampal neuronal loss.
 ...
PMID:Altered hippocampal kainate-receptor mRNA levels in temporal lobe epilepsy patients. 984 88

In the present study in situ hybridization was used to study the effect of kainic acid induced seizures on the expression of the zinc finger immediate-early genes (IEGs) NGFI-A, NGFI-B, NGFI-C, egr-2; egr-3 and Nurr1. Kainic acid markedly induced these IEGs especially in hippocampus, cortex and amygdala by 30 min. This induction gradually decreased and returned to baseline by 24 h in most regions. However, in the CA1 and CA3 subfields of hippocampus known to be damaged by kainic acid the expression of all the IEGs except egr-2 remained elevated for 24 h. NGFI-A, NGFI-B, NGFI-C and to a lesser extent, Nurr1, remained elevated also in the subcortical region of the temporal lobe. By 24 h incorporation of 14C-leucine decreased in the piriform cortex, amygdala, and in the CA1 and CA3 subfields, but not in CA2 and dentate gyrus. These areas showing decreased protein synthesis in the hippocampus by 24 h showed prolonged IEG induction, whereas IEG expression returned to control levels in areas showing normal protein synthesis. In the temporal lobe decreased protein synthesis coexisted with decreased IEG expression, whereas areas in the vicinity of the region showing decreased protein synthesis demonstrated elevated IEG expression. The decreased protein synthesis was localized in areas where extensive neuronal death has occurred. This prolonged IEG induction in the hippocampus, which has been linked with neuronal death, could solely represent a prolonged mRNA turnover caused by disrupted protein synthesis. The prolonged IEG expression in the temporal lobe appeared to be localized in regions where the cells are in stress, but still viable. The sustained IEG expression might therefore either represent a stress response by which the neurons are trying to protect themselves or, alternatively, the IEG response may be an early sign indicating that these cells are initiating a pathway leading to programmed cell death.
 ...
PMID:Prolonged expression of zinc finger immediate-early gene mRNAs and decreased protein synthesis following kainic acid induced seizures. 998 7

Cholinergic receptor agonists nicotine (nicotinic), carbachol (nicotinic/muscarinic) and pilocarpine (muscarinic) were administered into the hippocampus and mRNA levels of neurotrophins and their receptors determined using in situ hybridisation. Drug doses were carefully chosen to avoid the potentially confounding effects of seizure and cell death. Nicotine caused a long-lasting increase in nerve growth factor (NGF) mRNA in all subfields of the hippocampus. The increase was evident from 24 h up to 72 h after drug administration. This increase was dependent on excitatory amino acid neurotransmission as it was blocked by administration of an AMPA or NMDA receptor antagonist. In contrast, carbachol and pilocarpine produced a transient increase in NGF mRNA levels present 4-8 h after drug administration. Pilocarpine caused a transient increase in hippocampal brain-derived neurotrophic factor (BDNF) levels, with carbachol and nicotine showing the same trend. Nicotine and carbachol caused transient decreases in NT-3 mRNA levels in dentate gyrus and CA2 with pilocarpine showing a similar trend. Increases in mRNA encoding full-length trkB were seen 8 h after nicotine, with nicotine also causing elevations in a mRNA encoding a truncated isoform (trkB.T2). TrkC mRNA was not altered by any of the conditions used. The study suggests that muscarinic and nicotinic receptor activation in the hippocampus causes transient changes in all of the neurotrophins, but that NGF levels are selectively up-regulated by nicotinic receptor stimulation. The reciprocal interaction between NGF and ascending cholinergic systems may be a component of the cognitive enhancing effects of nicotine.
 ...
PMID:Hippocampal neurotrophin and trk receptor mRNA levels are altered by local administration of nicotine, carbachol and pilocarpine. 1010 Dec 39

By means of differential display techniques, we have previously identified an mRNA transcript whose expression is highly induced in the rat hippocampus by kainate-elicited seizures. Here, we report the cloning of a corresponding cDNA encoding a 55-amino-acid, serine-rich peptide which contains four predicted phosphorylation sites. The peptide was designated CaMK-related peptide (CARP) as it shares significant amino acid sequence identity with part of a novel putative calcium/calmodulin-dependent kinase (CaMK-VI) that was also cloned in this study. It appears that CARP and CaMK-VI are derived from the same gene through differential splicing. Intriguingly, CARP also exhibits 64% amino acid sequence identity with the C-terminal part of human doublecortin, encoded by a recently identified gene which is mutated in patients with X-linked lissencephaly and the double-cortex syndrome. In addition, the structure of CARP resembles the autoinhibitory, serine-rich N-terminal domain of CaMK-IV, suggesting a possible modulatory role of CARP with respect to CaMK activity. Northern blot analysis and in situ hybridization experiments showed that CARP mRNA is specifically induced by kainate-elicited seizures in the dentate gyrus and in the pyramidal layers CA1 and CA2, but not in CA3. In contrast, kainate-induced seizures did not change the level of expression of the CaMK-VI gene. We propose that CARP induction leads to the modulation of kinase activity in specific subregions of the rat hippocampus, providing a negative feedback mechanism for seizure-induced kinases.
 ...
PMID:Kainate-elicited seizures induce mRNA encoding a CaMK-related peptide: a putative modulator of kinase activity in rat hippocampus. 1021 52

4-Aminopyridine is a powerful convulsant that induces the release of neurotransmitters, including glutamate. We report the effect of intrahippocampal administration of 4-aminopyridine at six different concentrations through microdialysis probes on EEG activity and on concentrations of extracellular amino acids and correlate this effect with histological changes in the hippocampus. 4-Aminopyridine induced in a concentration-dependent manner intense and frequent epileptic discharges in both the hippocampus and the cerebral cortex. The three highest concentrations used induced also a dose-dependent enhancement of extracellular glutamate, aspartate, and GABA levels and profound hippocampal damage. Neurodegenerative changes occurred in CA1, CA3, and CA4 subfields, whereas CA2 was spared. In contrast, microdialysis administration of a depolarizing K+ concentration and of tetraethylammonium resulted in increased amino acid levels but no epileptic activity and no or moderate neuronal damage. These results suggest that seizure activity induced by 4-aminopyridine is due to a combined action of excitatory amino acid release and direct stimulation of neuronal firing, whereas neuronal death is related to the increased glutamate release but is independent of seizure activity. In addition, it is concluded that the glutamate release-inducing effect of 4-aminopyridine results in excitotoxicity because it occurs at the level of nerve endings, thus permitting the interaction of glutamate with its postsynaptic receptors, which is probably not the case after K+ depolarization.
 ...
PMID:Relationships among seizures, extracellular amino acid changes, and neurodegeneration induced by 4-aminopyridine in rat hippocampus: a microdialysis and electroencephalographic study. 1021 78

Recent evidence suggests an important role for NO in cholinergic models of epilepsy. Nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd), a marker of NO containing neurons, was shown to intensely colocalize with GABA in double-labeling studies performed in the hippocampal formation (exception made for the pyramidal cell layer) (Valtschanoff et al., J Comp Neurol 1993:331:111-121). In this sense, it further characterizes an extremely important cell category due to the relevant involvement of inhibitory systems in the mechanisms of genesis and propagation of seizures. Here, we assessed the histochemistry for NADPHd in the hippocampal complex of chronic pilocarpine-epileptic animals. NADPHd-positive cells were lost in almost every hippocampal subfield in pilocarpine-treated rats. The central portion of the polymorphic layer of the dentate gyrus (hilus) presented one of the highest losses of NADPHd-positive cells (55-79%) in the hippocampus. A significant loss of NADPHd-positive cells was seen in strata oriens, pyramidale, and radiatum CA1, CA2, and CA3 subfields. NADPHd staining in the subicular pyramidal cell layer was not different from that observed in controls. A significant loss of NADPHd-stained cells was observed in entorhinal cortex layers II and III in the epileptic group. For entorhinal cortex layers V and VI, however, results varied from an almost complete tissue destruction to an overexpression of NADPHd-positive cells, as well as an increase in neuropil staining. In summary, loss of NADPHd staining was not uniform throughout the hippocampal formation. There has been a growing support for the notion that GABAergic neurons in the hippocampal formation are not equally sensitive to insults. Our results suggest that, as a marker for a subpopulation of GABAergic neurons, NADPHd helps in further refining the characterization of the different neuronal populations sensitive to epileptic activity.
 ...
PMID:Loss of NADPH diaphorase-positive neurons in the hippocampal formation of chronic pilocarpine-epileptic rats. 1040 44

Changes in the subunit stoichiometry of the N-methyl-D-aspartate (NMDA) receptor (NMDAR) alters its channel properties, and may enhance or reduce neuronal excitability in temporal lobe epilepsy patients. This study determined whether hippocampal NMDA receptor subunit mRNA levels were increased or decreased in temporal lobe epilepsy patients compared with nonseizure autopsy cases. Hippocampal sclerosis (HS; n = 16), non-HS (n = 10), and autopsy hippocampi (n = 9) were studied for NMDAR1 (NR1) and NR2A-D mRNA levels by using semiquantitative in situ hybridization techniques, along with neuron densities. Compared with autopsy hippocampi, non-HS and HS patients showed increased NR2A and NR2B hybridization densities per dentate granule cell. Furthermore, non-HS hippocampi showed increased NR1 and NR2B mRNA levels per CA2/3 pyramidal neuron compared with autopsy cases. HS patients, by contrast, showed decreased NR2A hybridization densities per CA2/3 pyramidal neuron compared with non-HS and autopsy cases. These findings indicate that chronic temporal lobe seizures are associated with differential changes in hippocampal NR1 and NR2A-D hybridization densities that vary by subfield and clinical-pathological category. In temporal lobe epilepsy patients, these findings support the hypothesis that in dentate granule cells NMDA receptors are increased, and excitatory postsynaptic potentials should be strongly NMDA mediated compared with nonseizure autopsies. HS patients, by comparison, showed decreased pyramidal neuron NR2A mRNA levels, and this suggests that NMDA-mediated pyramidal neuron responses should be reduced in HS patients compared with non-HS cases.
 ...
PMID:Hippocampal N-methyl-D-aspartate receptor subunit mRNA levels in temporal lobe epilepsy patients. 1048 65

Northern epilepsy is an autosomal recessive childhood onset epilepsy syndrome, clinically characterized by generalized tonic-clonic seizures with onset at 5 to 10 years of age and subsequent slowly progressive mental deterioration. The patients may reach 50 or 60 years of age. A mutation responsible for the disease has recently been identified in a novel gene on chromosome 8p23, encoding a putative membrane protein with an unknown function. The present study, based on three autopsied patients, is the first neuropathological analysis of the disease, and showed intraneuronal accumulation of cytoplasmic autofluorescent granules. The granules were strongly stained by the Luxol fast blue, periodic acid-Schiff, and Sudan black B methods in paraffin sections, and were immunoreactive for subunit c of the mitochondrial ATP synthase and sphingolipid activator proteins A and D. The intraneuronal storage was highly selective: the third layer of the isocortex and the hippocampal CA2, CA3, and CA4 sectors were severely affected, while other layers of the isocortex, the CA1 sector, and the cerebellar cortex were only minimally involved. The membrane-bound storage cytosomes showed a curvilinear ultrastructure with admixture of some granular components. Western blotting and N-terminal sequence analysis of purified storage material identified subunit c as the major component. These findings establish Northern epilepsy as a new form of neuronal ceroid-lipofuscinosis with an exceptionally protracted course.
 ...
PMID:Northern epilepsy: a novel form of neuronal ceroid-lipofuscinosis. 1076 41

It is known that epilepsy patients diagnosed with neocortical temporal lobe epilepsy (NTLE), differ from those diagnosed with mesial temporal lobe epilepsy (MTLE), e.g., in hippocampal (HPC) pathology. In the present studies, we tested the hypothesis that NTLE and MTLE subtypes of human epilepsy might differ in regards to their HPC monoamine neurochemistry. Monoamine neurotransmitters were studied in separate signals and within s with semiderivative microvoltammetry, used in combination with stearate indicator, Ag-AgCl reference and stainless steel auxiliary microelectrodes. Anterior HPC specimens from the patients' epileptogenic zone, defined by electrocorticography, were resected neurosurgically from 13 consecutive patients with intractable temporal lobe epilepsy. Four patients were diagnosed with NTLE and nine with MTLE. The criteria for the diagnosis of NTLE versus MTLE was absence versus presence of HPC sclerosis, respectively, based on MRI examination of resected tissue. In addition, NTLE patients demonstrated seizure onset in anterolateral temporal neocortex on electroencephalography (EEG). HPC subparcellations studied were: (a) Granular Cells of the Dentate Gyrus (DG), (b) Polymorphic Layer of DG and (c) Pyramidal Layer: subfields, CA1 and CA2. Dopamine (DA), serotonin (5-HT), norepinephrine (NE) and ascorbic acid (AA) (co-factor in DA to NE synthesis), exhibited separate and characteristic half-wave potentials in millivolts. Each half-wave potential, i.e., the potential at which maximum current was generated, was experimentally established in vitro. Concentrations of neurotransmitters found in HPC subparcellations were interpolated from calibration curves derived in vitro from electrochemical detection of monoamines and AA in saline phosphate buffer. Significant differences between subtypes in concentration of monoamines were analyzed by the Mann Whitney rank sum test and those differences in probability distribution of monoamines were analyzed by the Fisher Exact test; in each case, P<0.01 was the criteria selected for determining statistical significance. DA concentrations were higher in NTLE compared with MTLE in each HPC subparcellation [P=0.037, 0.024 and 0.007, respectively (P<0.01)] and DA occurred more frequently in NTLE in the Pyramidal Layer [P=0.077 (P<0.01)]. AA was present in one NTLE patient. NE concentrations were higher in MTLE vs. NTLE in each subparcellation [P=0.012, 0.067 and 0.07, respectively (P<0.01)] and NE occurred more frequently in MTLE in Granular Cells of DG and Pyramidal Layer [P=0.052 and 0.014, respectively (P<0.01)]. In MTLE, NE concentrations in the CA1 subfield of the Pyramidal Layer were decreased vs. the CA2 subfield [P=0.063 (P<0.01)]. Serotonin was found in every HPC subparcellation of each subtype but 5-HT concentrations were higher in NTLE vs. MTLE in the Granular Cells of DG and the Pyramidal Layer (CA1 subfield) [P=0.076 and 0.095, respectively (P<0.01)]. Thus, this preliminary study showed that marked differences in HPC monoamine neurochemistry occurred in NTLE patients as compared with MTLE patients.
 ...
PMID:Monoamine neurotransmitters in resected hippocampal subparcellations from neocortical and mesial temporal lobe epilepsy patients: in situ microvoltammetric studies. 1099 35


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>