2014
DOI: 10.1126/scitranslmed.3007231
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Neonatal Estradiol Stimulation Prevents Epilepsy in Arx Model of X-Linked Infantile Spasms Syndrome

Abstract: Infantile spasms are a catastrophic form of pediatric epilepsy with inadequate treatment. In patients, mutation of ARX, a transcription factor selectively expressed in neuronal precursors and adult inhibitory interneurons, impairs cell migration and causes a major inherited subtype of the disease X-linked infantile spasms syndrome. Using an animal model, the Arx(GCG)10+7 mouse, we determined that brief estradiol (E2) administration during early postnatal development prevented spasms in infancy and seizures in … Show more

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Cited by 62 publications
(77 citation statements)
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“…In search of alternative therapy, the effects of estrogen, a neuroprotective hormone, were explored. Daily postnatal treatment of Arx (GCG)10+7 mutant mice for one week with the neurosteroid 17β-estradiol (E2), restored the decreased forebrain interneuron numbers, reduced neonatal spasms, and prevented seizures in adults [19]. E2 treatment was ineffective when administered to adults, indicating a critical, neonatal window in which E2 corrects pathological processes and modifies disease (Figure 2) [19].…”
Section: Estradiol Rescue Of Arx Mutations In Catastrophic Epilepsiesmentioning
confidence: 99%
See 1 more Smart Citation
“…In search of alternative therapy, the effects of estrogen, a neuroprotective hormone, were explored. Daily postnatal treatment of Arx (GCG)10+7 mutant mice for one week with the neurosteroid 17β-estradiol (E2), restored the decreased forebrain interneuron numbers, reduced neonatal spasms, and prevented seizures in adults [19]. E2 treatment was ineffective when administered to adults, indicating a critical, neonatal window in which E2 corrects pathological processes and modifies disease (Figure 2) [19].…”
Section: Estradiol Rescue Of Arx Mutations In Catastrophic Epilepsiesmentioning
confidence: 99%
“…Daily postnatal treatment of Arx (GCG)10+7 mutant mice for one week with the neurosteroid 17β-estradiol (E2), restored the decreased forebrain interneuron numbers, reduced neonatal spasms, and prevented seizures in adults [19]. E2 treatment was ineffective when administered to adults, indicating a critical, neonatal window in which E2 corrects pathological processes and modifies disease (Figure 2) [19]. E2 acts on ERα and ERβ receptors located on the plasma membrane or in the cytoplasm, which then activate downstream pathways via transcriptional regulation or non-genomic mediated signaling [20].…”
Section: Estradiol Rescue Of Arx Mutations In Catastrophic Epilepsiesmentioning
confidence: 99%
“…Quinidine, a partial antagonist of KCNT1 has been used to treat children with this encephalopathy (Bearden et al 2014). Neonatal estradiol has been shown to have neuroprotective effects that alter the disease trajectory and prevent infantile spasms and seizures in the ARX model of catastrophic epilepsy (Olivetti et al 2014). Greater effort in developing drugs that target the genetic mutation is likely to lead to more personalized treatments.…”
Section: Novel Therapeuticsmentioning
confidence: 99%
“…Based on existing reports that estradiol may promote cell proliferation, neuronal migration, and differentiation (McCarthy 2008), a follow-up study investigated the therapeutic effects of neonatal estradiol administration in the Arx (GCG)10þ7 mouse (Table 4) (Olivetti et al 2014). Neonatal estradiol administration before the onset of spasms (PN3-10) restored the number of calbindin and NPY interneurons in the cerebral cortex, as well as cholinergic striatal neurons, and prevented spasms and subsequent epilepsy in their model.…”
Section: Animal Models Of Early-life Epilepsymentioning
confidence: 99%