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)

Using alpha- and beta- tubulin cDNA Probes and Northern blot hybridization technique, we analyzed the effect of intraperitoneally injected Qingyangshen (QYS), a traditional Chinese medicine with antiepileptic property, and diphenylhydrantoin sodium (DPH) on hippocampal alpha- and beta-tubulin gene expression during kainic acid (KA) induced chronic seizures. It was found that: 1) thirty days after intraperitoneal injection of KA, alpha- and beta-tubulin mRNAs in animals showing chronic seizures increased 3.02 +/- 1.05 and 4.07 +/- 1.32 times respectively compared with control; 2) neither QYS (15 mg/kg, q.o.d. x 6) nor DPH (50 mg/kg, q.o.d. x 6), when used separately, could inhibit the above mentioned effect of KA; 3) when QYS (15 mg/kg, q.o.d. x 6) and DPH (50 mg/kg, q.o.d. x 6) were given in combination, the long-term increase in tubulin gene expression induced by KA was significantly reduced, with alpha- and beta-tubulin mRNAs being decreased to 0.44 +/- 0.08 and 0.50 x 0.10 times of corresponding values in animals treated with KA alone. The results indicate that the mechanism of antiepileptic effect of QYS is at least partially related to the inhibition of tubulin synthesis and subsequent reduction in mossy fiber sprouting and neosynaptogenesis.
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PMID:Effect of qingyangshen on hippocampal alpha- and beta-tubulin gene expression during kainic acid induced epileptogenesis. 813 79

The dentate granule cell layer of the rodent hippocampal formation has the distinctive property of ongoing neurogenesis that continues throughout adult life. In both human temporal lobe epilepsy and rodent models of limbic epilepsy, this same neuronal population undergoes extensive remodeling, including reorganization of mossy fibers, dispersion of the granule cell layer, and the appearance of granule cells in ectopic locations within the dentate gyrus. The mechanistic basis of these abnormalities, as well as their potential relationship to dentate granule cell neurogenesis, is unknown. We used a systemic chemoconvulsant model of temporal lobe epilepsy and bromodeoxyuridine (BrdU) labeling to investigate the effects of prolonged seizures on dentate granule cell neurogenesis in adult rats, and to examine the contribution of newly differentiated dentate granule cells to the network changes seen in this model. Pilocarpine-induced status epilepticus caused a dramatic and prolonged increase in cell proliferation in the dentate subgranular proliferative zone (SGZ), an area known to contain neuronal precursor cells. Colocalization of BrdU-immunolabeled cells with the neuron-specific markers turned on after division, 64 kDa, class III beta-tubulin, or microtubule-associated protein-2 showed that the vast majority of these mitotically active cells differentiated into neurons in the granule cell layer. Newly generated dentate granule cells also appeared in ectopic locations in the hilus and inner molecular layer of the dentate gyrus. Furthermore, developing granule cells projected axons aberrantly to both the CA3 pyramidal cell region and the dentate inner molecular layer. Induction of hippocampal seizure activity by perforant path stimulation resulted in an increase in SGZ mitotic activity similar to that seen with pilocarpine administration. These observations indicate that prolonged seizure discharges stimulate dentate granule cell neurogenesis, and that hippocampal network plasticity associated with epileptogenesis may arise from aberrant connections formed by newly born dentate granule cells.
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PMID:Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. 913 93

We report a case of a 15-year-old girl with new onset seizures, who had a mixed dysembryoplastic neuroepithelial tumor (DNT) and ganglioglioma of the right parieto-occipital lobe. The tumor appeared well demarcated and exhibited a low T1 and a high T2 signal on magnetic resonance imaging. Architecturally it was in large part intracortical and multinodular, but also featured a leptomeningeal component. The former corresponded to DNT, a proliferation of oligodendroglia-like cells (OLCs) arranged in nodules, as well as comprising a diffuse internodular element featuring "floating neurons" in a mucoid matrix. The leptomeningeal portion of the lesion was a ganglioglioma consisting of large neurons and astrocytes in association with marked desmoplasia. Spatially, the two components abutted one another but appeared distinct. Immunohistochemistry showed the neurons of the ganglioglioma to be positive for class III beta-tubulin, synaptophysin, and chromogranin A, whereas the astrocytic cells stained only for glial fibrillary acidic protein. Most OLCs in the DNT were positive for S-100 protein. This apparently mixed lesion suggests that a close histogenetic relationship exists between DNT and ganglioglioma. We postulate that the pluripotential progenitor cells residing in the subpial granular layer may have given rise to the cortical DNT and to the leptomeningeal ganglioglioma. To our knowledge, this is the first detailed histological, immunochemical and ultrastructural report of a mixed DNT and ganglioglioma.
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PMID:Mixed dysembryoplastic neuroepithelial tumor and ganglioglioma. 965 Jul 58

The extracellular homeostasis of glutamate in the brain is maintained by the efficient uptake into astroglial cells. The high extracellular glutamate levels seen during seizures are therefore probably a result of both an increased synaptic release and a deranged glutamate uptake. In this study we used immuno-blotting technique to measure the cortical levels of the astrocytic glutamate transport protein (GLT-1) and of the glutamate and aspartate transporting protein (GLAST) in an epilepsy model induced by ferrous chloride injection in the cortex of rats. The levels of GLT-1 were lower in epileptic rats than in controls, day 1 and 5 after induction, but not at 3 months. Glial fibrillary protein (GFAP) levels increased with time in the epileptic model, whereas GLAST and beta-tubulin III remained unchanged compared to controls. The results suggest that the transient decrease of GLT-1 could play a role in epileptogenesis, while recurrent seizure activity may be maintained by other mechanisms.
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PMID:Decreased cortical levels of astrocytic glutamate transport protein GLT-1 in a rat model of posttraumatic epilepsy. 1096 60

Pleomorphic xanthoastrocytoma (PXA) is an uncommon tumor, often seizure-associated and occurring in the temporal lobe of young adults. Although its cells are considered astrocytic in nature, recent studies suggest the presence of neuronal differentiation and a possible relationship to glioneuronal neoplasms. We immunostained 40 cases of PXA, including two composite PXA-gangliogliomas (PXA-GG), with a panel of glial (glial fibrillary acidic protein, S-100 protein) and neuronal markers (class III beta-tubulin, synaptophysin, neurofilament proteins, MAP2, and chromogranin A). Conventional PXAs demonstrated immunoreactivity for glial fibrillary acidic protein (100% of cases), S-100 protein (100%), class III beta-tubulin (73%), synaptophysin (38%), NF proteins (18 and 8%), and MAP2 (8%). Chromogranin A stain was absent in all conventional PXA cases. Neoplastic ganglion cells in both PXA-GGs stained with class III beta-tubulin, synaptophysin, and chromogranin A. Ultrastructural studies, performed in nine cases, demonstrated neuronal features including microtubules, dense core granules, and/or clear vesicles largely limited to cell processes (two PXAs) and in the cytoplasm (PXA component of one PXA-GG). Although the essential nature of PXA is clearly and uniformly glial, the significance of the limited neuronal differentiation is unclear, as it is the relationship between conventional PXA and PXA-GG. We found no evidence that the former is a precursor of the latter.
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PMID:Immunophenotype of pleomorphic xanthoastrocytoma. 1191 26

Protein L-isoaspartyl methyltransferase (PIMT) repairs the damaged proteins which have accumulated abnormal aspartyl residues during cell aging. Gene targeting has elucidated a physiological role for PIMT by showing that mice lacking PIMT died prematurely from fatal epileptic seizures. Here we investigated the role of PIMT in human mesial temporal lobe epilepsy. Using surgical specimens of hippocampus and neocortex from controls and epileptic patients, we showed that PIMT activity and expression were 50% lower in epileptic hippocampus than in controls but were unchanged in neocortex. Although the protein was down-regulated, PIMT mRNA expression was unchanged in epileptic hippocampus, suggesting post-translational regulation of the PIMT level. Moreover, several proteins with abnormal aspartyl residues accumulate in epileptic hippocampus. Microtubules component beta-tubulin, one of the major PIMT substrates, had an increased amount (two-fold) of L-isoaspartyl residues in the epileptic hippocampus. These results demonstrate that the down-regulation of PIMT in epileptic hippocampus leads to a significant accumulation of damaged tubulin that could contribute to neuron dysfunction in human mesial temporal lobe epilepsy.
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PMID:Down-regulation of protein L-isoaspartyl methyltransferase in human epileptic hippocampus contributes to generation of damaged tubulin. 1239 May 20

Tubulinopathies are a heterogeneous group of conditions with a wide spectrum of clinical severity resulting from variants in genes of the tubulin superfamily. Variants in TUBG1 have been described in three patients with posterior predominant pachygyria and microcephaly. We here report eight additional patients with four novel heterozygous variants in TUBG1 identified by next-generation sequencing (NGS) analysis. All had severe motor and cognitive impairment and all except one developed seizures in early life. The core imaging features included a pachygyric cortex with posterior to anterior gradient, enlarged lateral ventricles most pronounced over the posterior horns, and variable degrees of reduced white matter volume. Basal ganglia, corpus callosum, brainstem, and cerebellum were often normal, in contrast to patients with variants in other tubulin genes where these structures are frequently malformed. The imaging phenotype associated with variants in TUBG1 is therefore more in line with the phenotype resulting from variants in LIS1 (a.k.a. PAFAH1B1). This difference may, at least in part, be explained by gamma-tubulin's physiological function in microtubule nucleation, which differs from that of alpha and beta-tubulin.
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PMID:Tubulinopathies continued: refining the phenotypic spectrum associated with variants in TUBG1. 2970 37