Independent Neuronal Origin of Seizures and Behavioral Comorbidities in an Animal Model of a Severe Childhood Genetic Epileptic Encephalopathy

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Childhood epilepsy syndromes, such as the early epileptic encephalopathies (EE’s) encompass seizure disorders that manifest early and negatively impact or completely block developmental progression. Recently, mutations in DNM1 (dynamin 1) have been implicated in two EE syndromes, Lennox-Gastaut Syndrome and Infantile Spasms. Dynamin 1 is a large multimeric protein that is critical for electro-chemical communication between neurons. To understand the relationship between severe seizures and the cognitive and behavioral developmental outcomes in DNM1 patients, we focus on “fitful” mice that carry a mutation in the dynamin 1 gene. Fitful mice have an EE disorder that is highly reminiscent of the documented human patients. Here, we describe genetic manipulations in the mice that allow us to determine that the seizure activity has independent cellular origins from the developmental and behavioral consequences. This separation confirms that the seizures do not cause the severe developmental delay and abnormal behaviors in this animal model and further suggests that any treatments aimed at controlling the seizures per se may not be effective for some of the most acute neurobehavioral symptoms in these patients.

Vyšlo v časopise: Independent Neuronal Origin of Seizures and Behavioral Comorbidities in an Animal Model of a Severe Childhood Genetic Epileptic Encephalopathy. PLoS Genet 11(6): e32767. doi:10.1371/journal.pgen.1005347
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005347

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