SCN1A and Dravet syndrome

Rosch, Richard; Goldberg, Ethan M.

doi:10.1016/b978-0-323-89932-1.00015-9

Cited by 2 publications

(1 citation statement)

References 114 publications

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“…JCI Insight 2023;8 (15):e170399 https://doi.org/10.1172/jci.insight.170399 neocortices (17)(18)(19). However, their dysfunction preferentially impacts specific neuronal populations, such as fast-spiking inhibitory neurons owing to their predominant reliance on Scn1a/Nav1.1-containing channels (20)(21)(22). Gain-of-function SCNA1 mutations have been identified in rare genetic DEE and familial hemiplegic migraine type 3 (FHM3) patients (23,24), and increased SD susceptibility has been reported in the knockin mouse models (25,26).…”

Section: Introductionmentioning

confidence: 99%

A hyperthermic seizure unleashes a surge of spreading depolarizations in Scn1a-deficient mice

Aiba,

Ning,

Noebels

2023

JCI Insight

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Section: Introductionmentioning

confidence: 99%

A hyperthermic seizure unleashes a surge of spreading depolarizations in Scn1a-deficient mice

Aiba,

Ning,

Noebels

2023

JCI Insight

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A hyperthermic seizure unleashes a surge of spreading depolarizations inScn1adeficient mice

Aiba

Ning

Noebels

2022

Preprint

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Objective: Spreading depolarization (SD) is a massive wave of cellular depolarization that slowly migrates across brain gray matter. SD is frequently generated following brain injury and is associated with various acute and chronic neurological deficits. Here we report that spontaneous cortical SD waves are a common EEG abnormality in the Scn1a deficient mouse model (Scn1a+/R1407X). Method: Chronic DC-band EEG recording detected SDs, seizures, and seizure-SD complexes during prolonged monitoring in awake adult Scn1a+/R1407X mice. The effect of hyperthermic seizure and memantine was tested. Results: The spontaneous incidence of events is low and varied among animals, but SDs outnumber seizures. SD waves almost always spread unilaterally from parietal to frontal cortex. On average, spontaneous SD frequency robustly increased by 4.2-fold following a single hyperthermia-evoked seizure, persisting for days to a week without altering the kinetics of individual events. Combined video image and electromyogram analyses revealed that a single interictal SD is associated with prodromal motor activation followed by minutes-lasting immobility upon invasion of frontal cortex. Similar behavioral sequelae also appeared during postictal SD. Memantine treatment was effective in preventing SD exacerbation when given before and after the hyperthermic seizure, suggesting chronic activation of NMDA-receptor contributed to the prolonged SD aftermath. Interpretation: Our results reveal that cortical SD is a prominent electro-behavioral phenotype in this Scn1a deficient mouse model, and SD frequency is robustly sensitive to hyperthermic seizure induced mechanisms likely involving excess NMDAR signaling. The high susceptibility to SD may contribute to co-morbid pathophysiology in developmental epileptic encephalopathy.

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SCN1A and Dravet syndrome

Cited by 2 publications

References 114 publications

A hyperthermic seizure unleashes a surge of spreading depolarizations in Scn1a-deficient mice

A hyperthermic seizure unleashes a surge of spreading depolarizations in Scn1a-deficient mice

A hyperthermic seizure unleashes a surge of spreading depolarizations inScn1adeficient mice

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