ABSTRACT
Tuberous sclerosis complex (TSC), caused by dominant mutations in either TSC1 or TSC2 tumour suppressor genes is characterized by the presence of brain malformations, the cortical tubers that are thought to contribute to the generation of pharmacoresistant epilepsy. Here we report that tuberless heterozygote Tsc1(+/-) mice show functional upregulation of cortical GluN2C-containing N-methyl-D-aspartate receptors (NMDARs) in an mTOR-dependent manner and exhibit recurrent, unprovoked seizures during early postnatal life (Subject(s)
Anticonvulsants/pharmacology
, Epilepsy/drug therapy
, Pyrazoles/pharmacology
, Quinolones/pharmacology
, Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors
, TOR Serine-Threonine Kinases/genetics
, Tuberous Sclerosis/drug therapy
, Tumor Suppressor Proteins/genetics
, Action Potentials/drug effects
, Animals
, Disease Models, Animal
, Electroencephalography
, Epilepsy/genetics
, Epilepsy/metabolism
, Epilepsy/pathology
, Gene Expression Regulation
, Heterozygote
, Humans
, Male
, Mice
, Mice, Transgenic
, Microtomy
, Neocortex/drug effects
, Neocortex/metabolism
, Neocortex/pathology
, Patch-Clamp Techniques
, Receptors, N-Methyl-D-Aspartate/genetics
, Receptors, N-Methyl-D-Aspartate/metabolism
, Signal Transduction
, TOR Serine-Threonine Kinases/metabolism
, Tissue Culture Techniques
, Tuberous Sclerosis/genetics
, Tuberous Sclerosis/metabolism
, Tuberous Sclerosis/pathology
, Tuberous Sclerosis Complex 1 Protein
, Tumor Suppressor Proteins/deficiency
