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investigating the mechanisms involved in aberrant neurosphere migration in schizophrenia (784.2)
Author(s) -
Patruno Anna,
Tran Ngoc,
Abdelrahim Mohammed,
Brennand Kristen
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.784.2
Subject(s) - neurosphere , schizophrenia (object oriented programming) , neuropathology , neural stem cell , induced pluripotent stem cell , progenitor cell , neurogenesis , neuroscience , reprogramming , biology , disease , microbiology and biotechnology , stem cell , medicine , cell , genetics , cellular differentiation , pathology , psychiatry , adult stem cell , gene , embryonic stem cell
Schizophrenia (SCZD) is a chronic, debilitating disorder with a prevalence of 1% and typically appears in the late adolescent and early adulthood years. Postmortem studies have been pivotal in understanding the neuropathology of schizophrenic brains by revealing characteristics such as reduced cell size, brain volume and neuronal connections; however, the cellular and molecular mechanisms involved in the disease as well as its development remain unclear. To investigate disease progression, we modeled genetic predisposition to SCZD by reprogramming fibroblasts from SCZD patients into human induced pluripotent stems cells (hiPSCs) and differentiating these cells into neural progenitor cells (NPCs) and neurons. Using a neurosphere migration assay, we observed aberrant migration of SCZD NPCs in vitro. To investigate the mechanism responsible for this aberrant migration, we manipulated the RHO‐ROCK (Rho‐associated kinase) signaling pathway in SCZD NPCs. In addition, we investigated whether treatment with antipsychotics such as Loxapine and Clozapine was sufficient to ameliorate aberrant migration. Neurosphere migration assays are a useful model to study molecular mechanisms in SCZD as well as disease predisposition, which may contribute in developing potential treatments. Grant Funding Source : Supported by NYSCF and NIH/NIMH, R01 MH101464