Synaptic defects in human neurons derived from Autism Spectrum Disorders

Title Synaptic defects in human neurons derived from Autism Spectrum Disorders
Lecturer Dr. Alysson Renato Muotri(University of California San Diego)
Language English
Date&Time 08/03/2012 (Fri) 16:00~17:00
Venue D105
Autism spectrum disorders (ASD) are complex neurodevelopmental diseases in which different combinations of genetic mutations may contribute to the phenotype. Using Rett syndrome (RTT) as an ASD genetic model, we developed a culture system using induced pluripotent stem cells (iPSCs) from RTT patients’ fibroblasts. RTT patients’ iPSCs are able to undergo X-inactivation and generate functional neurons. Neurons derived from RTT-iPSCs had fewer synapses, reduced spine density, smaller soma size, altered calcium signaling and electrophysiological defects when compared to controls. RTT neurons were also used to test the effects of drugs in rescuing synaptic defects (Marchetto et al, Cell 2010). Finally, RTT-iPSC differentiated into neural precursor cells supported an increase amount of somatic mutations caused by de novo L1 insertions (Muotri et al, Nature 2010). To identify common cellular and molecular pathways involved in autism, we derived neurons from other ASD-iPSCs. Interestingly, similarly to RTT-neurons, we also observed defects in a subset of ASD neurons. These data suggest that perturbation in common molecular pathways can lead to neuronal alterations involved in the etiology of ASDs. The overlap phenotypes observed in the iPSC-derived human neurons between ASD patients provide evidence of an unexplored developmental window, before disease onset, where potential therapies could be successfully employed. Our model recapitulates early stages of a human neurodevelopmental disease and represents a promising cellular tool for drug screening, diagnosis and personalized treatment.
Contact 分子神経分化制御
中島 欽一 (

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