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Molecular Mechanisms Underlying the Epileptogenesis and Seizure Progression in Tuberous Sclerosis Complex 1 Deficient Mouse Models

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Technical Report,15 Sep 2015,14 Sep 2018

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Columbia University New York United States

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We seek to understand four basic questions related to epileptogenesis 1 What is the role of mTOR dysregulation in epileptogenesis in the developing brain 2 What are the molecular mechanisms downstream of mTOR hyperactivation that trigger epileptogenesis in developing brains 3 What are the long-term pharmacological treatments to prevent the development andor progression of seizures 4 What are biomarkers for epileptogenesis and the prognostic biomarkers for disease progression We have established a neuroglial tuberous sclerosis complex 1TSC1-deficient mouse model in which spontaneous seizures begin at 2.5 months of the age and progress into 7-8 months. This time course allows the analysis of molecular changes before and after the onset of spontaneous electrographic and behavioral seizures and provide reliable biomarkers for epileptogenesis and the progression of epilepsy. We have also developed a neuronal-specific mouse model, deleting Tsc1 by driving cre from the CAMKII promoter. We propose gene expression profiling, electrophysiological, biochemical, immunohistochemical and behavioral studies.

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  • Medicine and Medical Research

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