Disease relevance of El1

• The genetically epilepsy-prone rat has motor seizures in response to auditory stimuli [1].
• Clinical and genetic heterogeneity as well as influence of environmental factors have hampered identification of the genetic factors which are involved in episodic diseases such as migraine, episodic ataxia and epilepsy [2].
• These results suggest that an increase in the synthesis of QUI in the brain is involved in the pathogenesis of epileptic seizures in El mice [3].
• The compound has been causally related to various neurodegenerative disorders, including epilepsy [3].
• These findings suggest that an abnormality in PDGF-BB release may make El mice susceptible to tonic-clonic convulsions [4].

Psychiatry related information on El1

• A role for Zn2+ in a variety of neurological conditions such as stroke, epilepsy and Alzheimer's disease has been postulated [5].
• Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors [6].
• We show that these patients present with mental retardation, epilepsy and, in some cases, psychiatric features [7].
• Epilepsy is associated with significant neurological morbidity, including learning disabilities, motor deficits, and behavioral problems [8].
• Some HDIs are also commonly prescribed treatments for epilepsy and bipolar disorders [9].

High impact information on El1

• Stargazer mice have spike-wave seizures characteristic of absence epilepsy, with accompanying defects in the cerebellum and inner ear [10].
• Genetically epilepsy-prone rodent strains have been frequently used to examine the effect of genetic factors on seizure susceptibility [11].
• Ceruloplasmin gene defect associated with epilepsy in EL mice [12].
• Based on the similarity between the human and mouse genomes, mouse models of epilepsy could facilitate the discovery of genes associated with epilepsy syndromes [13].
• The findings are relevant to the basic mechanisms of epilepsy and to theories of genetic recombination and gene mapping [14].

Chemical compound and disease context of El1

• Local cerebral glucose utilization in epileptic seizures of the mutant El mouse [15].
• After the intracisternal injection of three protease inhibitors which prevent the degradation of methionine enkephalin (amastatin, Des-Pro2-bradykinin, and phosphoramidon) and a mixture of these protease inhibitors, we investigated the effect on convulsive seizures in the seizure-susceptible El mouse [16].
• Megimide-induced epileptic seizures were recorded in nine male El and six male ddY mice with the chronic implantation technique for monopolar recording of electrocorticogram (ECoG) [17].
• Phenobarbital (PB) (5, 25 and 50 mg/kg), which was administered intraperitoneally to evaluate the effect of it on El mice, inhibited convulsive seizures dose-dependently [18].
• Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1 [19].

Biological context of El1

• A previous genetic mapping study of EL backcrosses to the strains ABP/LeJ or DBA/2J showed two quantitative trait loci (QTL) with large effects on seizure frequency (El1, Chr 9; El2, Chr 2) and implied the existence of other QTL with lesser effects [20].
• The maximum Z-score for El1 (Chromosome 9) was 3.7 after 6 tests, but decreased to 2.4 after 15 tests [21].
• The location of El-1 on distal chromosome 9 may allow identification of an epilepsy candidate gene in humans on the basis of conserved synteny with human chromosome 3 [22].
• The underlying neuroanatomy involves hippocampal-cortical interactions indicative of a partial epilepsy [1].
• Since calcium channels are involved in numerous cellular functions, including proliferation and differentiation, membrane excitability, neurite outgrowth and synaptogenesis, signal transduction, and gene expression, their role in generating the absence epilepsy phenotype may be complex [23].

Anatomical context of El1

• Subchronic treatment with phenytoin (25 mg/kg per day) for 14 days increased the [3H]saxitoxin binding to brain-derived synaptic membranes of both El and control ddY mice in a time dependent manner [24].
• We conclude that increased synaptic vesicle glutamate uptake is brain-region specific (cerebrum) and is associated with the development or maintenance, rather than the initial cause, of seizures in the EL model of epilepsy [25].
• With the low-Mg(2+)-model of epilepsy, this study investigated the effect of electrical LTD, chemical LTD, and depotentiation on the susceptibility of the entorhinal cortex to epileptiform activity [26].
• The El mouse is an internationally registered animal model for hereditary temporal lobe epilepsy [27].
• The epileptic focus in El mice presumably exists in the hippocampus [15].

Associations of El1 with chemical compounds

• We investigated the effects of 17 beta-estradiol (E2) and progesterone (PG) on seizure sensitivity in two genetically epilepsy-prone strains, the DBA/2J and the C57/EL hybrid [28].
• No significant differences were found among the B6, DDY, and EL mice for the release of glutamate (23.0 +/- 2.0, 32.3 +/- 5.8, and 25.9 +/- 2.6, respectively) or GABA (23.5 +/- 0.7, 19.5 +/- 3.2, and 21.8 +/- 3.2, respectively) [29].
• Thus, enhanced aspartate release precedes the onset of EL seizures and may be related to the cause rather than to the effects of seizure activity [29].
• This increase plateaued at 21 +/- 4% in El mice and 28 +/- 3% in ddY control mice after administration of phenytoin for seven days [24].
• Effect of convulsions of the synthesis of heterogeneous nuclear RNA associated with polyadenylate and oligoadenylate sequences from El mouse brain as a convulsive strain [30].

Physical interactions of El1

• 6 The results indicate that in vivo, NMDA receptors are not maximally potentiated by endogenous glycine and suggest an important involvement of the glycine modulatory site on the NMDA receptor/ion channel complex in the pathophysiology of epilepsy [31].

Regulatory relationships of El1

• These findings show that the seizure-susceptible El mouse kindles more rapidly than the genetically similar but nonepileptic ddY control and suggest that an inherited seizure susceptibility accelerates the kindling rate [32].
• These results provide evidence that signaling through GFR alpha 2 is involved in mechanisms regulating the development and persistence of kindling epilepsy [33].
• Our data suggest that BDNF signaling may partly mediate the development of epilepsy and propose that regrowth or repair processes initiated by status epilepticus and promoted by BDNF signaling may not be as advantageous as previously thought [34].
• Involvement of Scn1b and Kcna1 ion channels in audiogenic seizures and PTZ-induced epilepsy [35].
• To establish a link between adenosine kinase expression and seizure activity, we analyzed the expression of adenosine kinase in the brain of control mice and in a kainic acid-induced mouse model of mesial temporal lobe epilepsy [36].

Other interactions of El1

• In this study, we cloned and sequenced the cDNA for 3-HAO and showed that its expression in the brain of El mice was higher than that of control ddY mice [37].
• These results confirm El2 as an important QTL and show that it has significant phenotypic effects in the absence of other EL-derived alleles, including El1 [38].
• Six seizure frequency quantitative trait loci (QTLs), El1-El6, were previously mapped in crosses between EL and non-epileptic strains using mechanical tossing procedures beginning at 30 days of age [21].
• The slow-wave epilepsy mouse phenotype is the result of loss of function of the ubiquitous sodium hydrogen exchanger NHEI [39].
• Thus, the GRY rat with P/Q-type Ca(2+) channel disorders is a useful model for studying absence epilepsy and Cacna1a-related diseases [40].

Analytical, diagnostic and therapeutic context of El1

• Animal models of inherited epilepsy [1].
• The genetic absence epilepsy rat has age-related spontaneous seizures characterized by motor arrest and head drops that are correlated with generalized spike-wave on the electroencephalogram (EEG) [1].
• After cessation of treatment with phenytoin, [3H]saxitoxin binding capacity returned to the basal level within two weeks in both ddY and El brains [24].
• To date, molecular cloning technologies has elucidated the primary basis of most of the known single locus epilepsy mutants [41].
• Brain distribution after i.v. injection of 65ZnCl2 into El mice, an animal model of genetically determined epilepsy, was studied by autoradiography to study the utilization of zinc in the brain [42].

References