iPSC as a model for investigating the impact of childhood adverse experiences on neurodevelopment in different ethnic backgrounds

• Grant number: 24/02709-1
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2024
• End date: November 30, 2025
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Ivaldo da Silva
• Grantee: Ivaldo da Silva
• Principal researcher abroad: Michael Ziller
• Institution abroad: University of Munster, Germany
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Andrea Parolin Jackowski
• Associated research grant: 19/21612-0 - Maternal adversity, inflammation, and neurodevelopment: how intergenerational processes perpetuate disadvantage in a low-resource setting, AP.TEM

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 babies 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. Our aim is to build a strong collaborative foundation for the development of a comparative research strategy that will be carried out across both sites (UNIFESP and University of Münster). 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. This collaborative approach will provide training/research opportunities for students and the identification of scientific journals and conferences, newspapers and other media to disseminate academic products as a result of this partnership. Thus, a team of researchers will identify external funding entities (national and international) and opportunities to support and the implementation of a research project in partnership (AU)