Modelling Prenatal Hypoxia As A Risk Factor For Schizophrenia Vulnerability In Patient-Derived Cerebral Organoids
type: CreativeWork
description: Prenatal hypoxia during fetal development is a significant environmental risk factor linked to schizophrenia (SCZ) vulnerability. However, hypoxia’s impact on human brain development at the cellular level remains unclear. Our laboratory has developed human cerebral organoids using induced pluripotent stem cells (iPSCs) derived from healthy control or SCZ patient cell lines to address these questions. This creates a platform that allows for the investigation into the pathophysiology of SCZ and hypoxia in tandem. Organoids were exposed to hypoxic conditions at one month of development, mimicking the early stages of cortical growth in the human fetus. Results reveal innate differences in neuronal development markers in SCZ organoids at the transcriptomic and protein level. In response to hypoxia, SCZ organoids exhibit dysregulation of mitochondrial-associated proteins and genes required for normal metabolism and growth. Our findings highlight critical differences in the expression of vital neuronal markers in SCZ and highlight hypoxia’s further impacts on neurodevelopmental pathophysiology related to SCZ risk.
abstract: Prenatal hypoxia during fetal development is a significant environmental risk factor linked to schizophrenia (SCZ) vulnerability. However, hypoxia’s impact on human brain development at the cellular level remains unclear. Our laboratory has developed human cerebral organoids using induced pluripotent stem cells (iPSCs) derived from healthy control or SCZ patient cell lines to address these questions. This creates a platform that allows for the investigation into the pathophysiology of SCZ and hypoxia in tandem. Organoids were exposed to hypoxic conditions at one month of development, mimicking the early stages of cortical growth in the human fetus. Results reveal innate differences in neuronal development markers in SCZ organoids at the transcriptomic and protein level. In response to hypoxia, SCZ organoids exhibit dysregulation of mitochondrial-associated proteins and genes required for normal metabolism and growth. Our findings highlight critical differences in the expression of vital neuronal markers in SCZ and highlight hypoxia’s further impacts on neurodevelopmental pathophysiology related to SCZ risk.
author: Gummerson, Dana M
language: en_ca
keywords: Cerebral organoid, Schizophrenia, Hypoxia, Mitochondrial dysfunction, Fetal brain development
date published: 2023-09-13
date modified: 2026-07-27T21:56:09Z
provider: Western University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: The University of Western Ontario

PropertyValue
property ID: Handle
value: https://hdl.handle.net/20.500.14721/37299