Chemoconvulsant‐induced Seizure Susceptibility: Toward a Common Genetic Basis?

Chaix, Yohan; Ferraro, Thomas N.; Lapouble, Eve; Martin, Benoı̂t

doi:10.1111/j.1528-1167.2007.01289.x

Cited by 10 publications

(8 citation statements)

References 44 publications

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“…Genetic analysis in reciprocal N2 backcrosses identified modifier loci on chromosomes 5, 7, 8 and 11 that influence the early lethality phenotype of the Scn1a +/− Dravet mouse model. This is consistent with previous studies that have demonstrated that seizure-related phenotypes are influenced by genetic factors (Chaix et al 2007;Frankel 2009;Schauwecker 2011;Seyfried et al 1999;Winawer et al 2007). In addition, it is consistent with previous results from our laboratory demonstrating that modifier genes influence epilepsy severity and survival in a mouse model with a mutation in the Scn2a voltage-gated sodium channel gene (Bergren et al 2005(Bergren et al , 2009Hawkins & Kearney 2012;Jorge et al 2011).…”

Section: Discussionsupporting

confidence: 93%

Mapping genetic modifiers of survival in a mouse model of Dravet syndrome

Miller

Hawkins

McCollom

et al. 2013

Genes Brain and Behavior

161

268

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Epilepsy is a common neurological disorder affecting approximately 1% of the population. Mutations in voltage-gated sodium channels are responsible for several monogenic epilepsy syndromes. More than 800 mutations in the voltage-gated sodium channel SCN1A have been reported in patients with generalized epilepsy with febrile seizures plus and Dravet syndrome. Heterozygous loss-of-function mutations in SCN1A result in Dravet syndrome, a severe infant-onset epileptic encephalopathy characterized by intractable seizures, developmental delays and increased mortality. A common feature of monogenic epilepsies is variable expressivity among individuals with the same mutation, suggesting that genetic modifiers may influence clinical severity. Mice with heterozygous deletion of Scn1a (Scn1a+/−) model a number of Dravet syndrome features, including spontaneous seizures and premature lethality. Phenotype severity in Scn1a+/− mice is strongly dependent on strain background. On the 129S6/SvEvTac strain Scn1a+/− mice exhibit no overt phenotype, while on the (C57BL/6J × 129S6/SvEvTac)F1 strain Scn1a+/− mice exhibit spontaneous seizures and early lethality. To systematically identify loci that influence premature lethality in Scn1a+/− mice, we performed genome scans on reciprocal backcrosses. QTL mapping revealed modifier loci on mouse chromosomes 5, 7, 8 and 11. RNA-seq analysis of strain-dependent gene expression, regulation and coding sequence variation provided a list of potential functional candidate genes at each locus. Identification of modifier genes that influence survival in Scn1a+/− mice will improve our understanding of the pathophysiology of Dravet syndrome and may suggest novel therapeutic strategies for improved treatment of human patients.

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Section: Discussionsupporting

confidence: 93%

Mapping genetic modifiers of survival in a mouse model of Dravet syndrome

Miller

Hawkins

McCollom

et al. 2013

Genes Brain and Behavior

161

268

View full text Add to dashboard Cite

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“…This suggests caution when interpreting verbal memory test scores of patients with high levels of anxiety, yet allows for greater confidence in verbal memory scores of patients with low anxiety levels. This is important not only for preoperative lateralization, but also in predicting postoperative changes since those with higher levels of pre-surgical verbal memory are more likely to experience a decline following surgery [15, 37, 38]. Thus, it would be important to determine whether low preoperative verbal memory scores truly reflect level of functioning and/or are confounded by high anxiety.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have found that verbal list learning memory was as good, and in some cases a better predictor of postoperative verbal memory than intracarotid amobarbital testing whereas this has not been found among visual measures. Those with problematic pre-surgical verbal memory were less likely to experience post-surgical declines, whereas those with higher presurgical verbal memory were more likely to experience a significant decline in verbal memory [15, 37, 38]. The problems with consistent visual memory assessment in TLE have not yet made such a prediction possible [8, 13–15].…”

Section: Introductionmentioning

confidence: 99%

Influence of anxiety on memory performance in temporal lobe epilepsy

Brown

Westerveld

Langfitt

et al. 2014

Epilepsy & Behavior

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This study examined the degree to which anxiety contributed to inconsistent material-specific memory difficulties among 243 temporal lobe epilepsy patients from the Multisite Epilepsy Study. Visual memory performance on the Rey Complex Figure Test (RCFT) was lower for those with high versus low level of anxiety, but was not found to be related to side of TLE. Verbal memory on the California Verbal Learning Test (CVLT) was significantly lower for left than right TLE patients with low anxiety, but equally impaired for those with high anxiety. These results suggest that we can place more confidence in the ability of verbal memory tests like the CVLT to lateralize to left TLE for those with low anxiety, but that verbal memory will be less likely to produce lateralizing information for those with high anxiety. This suggests that more caution is needed when interpreting verbal memory tests for those with high anxiety. These results indicated that RCFT performance was significantly affected by anxiety and did not lateralize to either side, regardless of anxiety level. This study adds to the existing literature which suggests that drawing-based visual memory tests do not lateralize among TLE patients, regardless of anxiety level.

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“…These long-term changes in plasticity that occur in surviving neurons induce essentially permanent alterations in these neurons that have been implicated in causing the long-term morbidity associated with AE (Delorenzo et al, 2005). The process of epileptogenesis may also be influenced by genetic predisposition (Scher, 2003;Chaix et al, 2007) and cause longterm genetic changes in the brain (Elliott et al, 2003;Lukasiuk et al, 2006). Understanding how these changes promote epileptogenesis and the development of AE is an important goal in developing rational therapeutic approaches to reducing the mortality and morbidity of AE.…”

Section: Introductionmentioning

confidence: 99%

Long-term decrease in calbindin-D28K expression in the hippocampus of epileptic rats following pilocarpine-induced status epilepticus

et al. 2008

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SummaryAcquired epilepsy (AE) is characterized by spontaneous recurrent seizures and long-term changes that occur in surviving neurons following an injury such as status epilepticus (SE). Long-lasting alterations in hippocampal Ca 2+ homeostasis have been observed in both in vivo and in vitro models of AE. One major regulator of Ca 2+ homeostasis is the neuronal calcium binding protein, calbindinD28k that serves to buffer and transport Ca 2+ ions. This study evaluated the expression of hippocampal calbindin levels in the rat pilocarpine model of AE. Calbindin protein expression was reduced over 50% in the hippocampus in epileptic animals. This decrease was observed in the pyramidal layer of CA1, stratum lucidum of CA3, hilus, and stratum granulosum and stratum moleculare of the dentate gyrus when corrected for cell loss. Furthermore, calbindin levels in individual neurons were also significantly reduced. In addition, the expression of calbindin mRNA was decreased in epileptic animals. Time course studies demonstrated that decreased calbindin expression was initially present 1 month following pilocarpine-induced SE and lasted for up to 2 years after the initial episode of SE. The results indicate that calbindin is essentially permanently decreased in the hippocampus in AE. This decrease in hippocampal calbindin may be a major contributing factor underlying some of the plasticity changes that occur in epileptogenesis and contribute to the alterations in Ca 2+ homeostasis associated with AE.

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Chemoconvulsant‐induced Seizure Susceptibility: Toward a Common Genetic Basis?

Cited by 10 publications

References 44 publications

Mapping genetic modifiers of survival in a mouse model of Dravet syndrome

Mapping genetic modifiers of survival in a mouse model of Dravet syndrome

Influence of anxiety on memory performance in temporal lobe epilepsy

Long-term decrease in calbindin-D28K expression in the hippocampus of epileptic rats following pilocarpine-induced status epilepticus

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