Neonatal estradiol stimulation prevents epilepsy in Arx model of X-linked infantile spasms syndrome
| Autor: | Jeffrey L. Noebels, Pedro R. Olivetti, Atul Maheshwari |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Spasm Interneuron Transcription Genetic Stimulation Biology Inhibitory postsynaptic potential Article Aicardi syndrome Epilepsy Mice Interneurons Internal medicine medicine Animals Estrogen Receptor beta Estrogen receptor beta Homeodomain Proteins Neurons Estradiol Estrogen Receptor alpha Electroencephalography General Medicine medicine.disease Aicardi Syndrome Disease Models Animal Endocrinology medicine.anatomical_structure Phenotype Mutation GABAergic Anticonvulsants Estrogen receptor alpha Spasms Infantile Transcription Factors |
| Zdroj: | Science translational medicine. 6(220) |
| ISSN: | 1946-6242 |
| Popis: | 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 adult mutants. E2 was ineffective when delivered after puberty or 30 days after birth. Early E2 treatment altered mRNA levels of three downstream targets of Arx (Shox2, Ebf3, and Lgi1) and restored depleted interneuron populations without increasing GABAergic synaptic density. Postnatal E2 treatment may induce lasting transcriptional changes that lead to enduring disease modification and could potentially serve as a therapy for inherited interneuronopathies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|