iPSC as a model for investigating the impact of early stress exposure on neurodevelopment

• Grant number: 24/15176-1
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: February 01, 2025
• End date: April 30, 2025
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Andrea Parolin Jackowski
• Grantee: Aline Camargo Ramos
• Supervisor: Michael Ziller
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: University of Munster, Germany
• Associated to the scholarship: 21/04819-0 - The intergerational impact of maternal exposure to childhood adversities on child cerebral development: regulation and functioning of the hpa axis as a resilience marker, BP.PD

Abstract

It is known that exposure to maternal stress impairs the neurogenesis of offspring by inducing life-long effects and culminating in cognitive and neuropsychiatric abnormalities in adulthood. Our previous results showed that infants born from mothers with higher levels of salivary cortisol during the early postnatal period exhibited lower hippocampal volume in the first month of life. Since studies in humans do not allow us to investigate the mechanisms related to the observed results, we aim to use iPSCs (induced pluripotent stem cells) for such an investigation. To this end, we will generate the co-culture of inhibitory and excitatory neurons, specifically GABAergic inhibitory interneurons and glutamatergic excitatory pyramidal neurons, and expose them to cortisol, mimicking the effects of intrauterine fetal exposure. Thus, we will explore neuronal survival and growth, the electrophysiologic phenotyping of the E/I balance, and functional genomic analyses. In this way, we aim to contribute to the elucidation of pathways and mechanisms related to the effects of perinatal exposure on the neurodevelopment of offspring.