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Convulsive seizures from experimental focal cortical dysplasia occur independently of cell misplacement
- Source :
- Nature Communications, Nature Communications, Vol 7, Iss 1, Pp 1-12 (2016)
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- Focal cortical dysplasia (FCD), a local malformation of cortical development, is the most common cause of pharmacoresistant epilepsy associated with life-long neurocognitive impairments. It remains unclear whether neuronal misplacement is required for seizure activity. Here we show that dyslamination and white matter heterotopia are not necessary for seizure generation in a murine model of type II FCDs. These experimental FCDs generated by increasing mTOR activity in layer 2/3 neurons of the medial prefrontal cortex are associated with tonic-clonic seizures and a normal survival rate. Preventing all FCD-related defects, including neuronal misplacement and dysmorphogenesis, with rapamycin treatments from birth eliminates seizures, but seizures recur after rapamycin withdrawal. In addition, bypassing neuronal misplacement and heterotopia using inducible vectors do not prevent seizure occurrence. Collectively, data obtained using our new experimental FCD-associated epilepsy suggest that life-long treatment to reduce neuronal dysmorphogenesis is required to suppress seizures in individuals with FCD.<br />The etiology of focal cortical dysplasia (FCD) is not fully understood. Here authors generate an mTORC1 overactivation mouse model that recapitulates hallmarks of type II FCDs, including spontaneous seizures, and suggest that neuronal defects, rather than macrostructural changes, lead to seizures.
- Subjects :
- Male
0301 basic medicine
Science
Green Fluorescent Proteins
Prefrontal Cortex
General Physics and Astronomy
Biology
Article
General Biochemistry, Genetics and Molecular Biology
White matter
Mice
03 medical and health sciences
Epilepsy
0302 clinical medicine
Cell Movement
Genes, Reporter
Seizures
medicine
Animals
Humans
Cognitive Dysfunction
Prefrontal cortex
PI3K/AKT/mTOR pathway
Neurons
Sirolimus
Multidisciplinary
TOR Serine-Threonine Kinases
General Chemistry
Cortical dysplasia
medicine.disease
White Matter
3. Good health
Malformations of Cortical Development
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Heterotopia (medicine)
Gene Expression Regulation
Female
Neuroscience
Neurocognitive
030217 neurology & neurosurgery
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....573a18d934baa50744e74197bb382b68