Judges’ Queries and Presenter’s Replies

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Presentation Discussion

  • Icon for: Sebastian Vega

    Sebastian Vega

    Trainee
    May 23, 2012 | 01:00 p.m.

    Nice presentation, I have a few questions/comments:

    1) What are the causes of schizophrenia? If it’s hereditary…
    2) Do you think someday an in vitro disease model using reprogrammed fibroblasts from schizophrenic patients could be used to determine a truly personalized treatment regime?

  • Icon for: Kristina Hernandez

    Kristina Hernandez

    Presenter
    May 24, 2012 | 10:28 p.m.

    Thanks!
    1)Schizophrenia displays a complex pattern of inheritance, suggesting the involvement of multiple genetic factors in combination with environmental factors. Modern molecular genetic studies have identified a number of possible genetic risk factors for schizophrenia, including the NOS1AP gene. Single nucleotide polymorphisms within NOS1AP have been found to be significantly associated with schizophrenia.
    2)I am currently working with induced pluripotent stem cells that were generated from fibroblasts taken from patients with schizophrenia and the associated NOS1AP SNPs. I hope to find a biomarker for the disease as well as test drugs that may be more beneficial to patients with the NOS1AP SNP. So yes I do believe that personalized medicine for patients with such a complex disorder is necessary and within reach.

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Icon for: Kristina Hernandez

KRISTINA HERNANDEZ

Rutgers University
Years in Grad School: 4

Both a schizophrenia susceptibility gene, NOS1AP, and an antipsychotic agent, clozapine, stunt dendrite development in human iPSC-derived neurons

Abnormal dendritic arbor development has been implicated in a number of neurodevelopmental disorders, such as autism and Rett syndrome, as well as the neuropsychiatric disorder schizophrenia. NOS1AP, a protein encoded by a schizophrenia susceptibility gene, is an intracellular factor that alters neuronal morphology and synaptic structures. Brain samples from subjects with schizophrenia have elevated levels of NOS1AP in the DLPFC, a region of the brain associated with cognitive function. Furthermore, we previously reported that NOS1AP negatively regulates dendrite branching in rat hippocampal neurons. For patients with the NOS1AP schizophrenia risk factor, the cognitive deficits could be linked to neurodevelopmental defects. To investigate the role that NOS1AP plays in human dendritic arbor development, we used human iPSC technology to generate human neurons. We found that increased protein levels of NOS1AP decrease dendrite branching in human neurons at the developmental time point when both primary and secondary branching actively occurs. Next, we tested whether an antipsychotic drug is able to restore normal dendritogenesis in these human neurons. Preliminary results suggest that the antipsychotic agent clozapine decreases dendrite branching in the developing human neurons, both alone and when in combination with increased NOS1AP protein levels. Our studies show how an in vitro model of a schizophrenia vulnerability factor could be used as a platform to screen drugs for preventative therapies. In addition, this in vitro model of human dendrite development can be used to determine whether prenatal exposure to drugs that act in the CNS produce potentially lasting adverse effects on fetal neurodevelopment.