Project Description

Challenge

Children are usually school-aged by the time they receive a diagnosis for Fetal Alcohol Spectrum Disorder. However, evidence indicates that early intervention is beneficial. Having reliable biomarkers to detect changes related to prenatal alcohol exposure (PAE) could allow clinicians to identify FASD in children at a younger age and therefore provide earlier access to supports.

Project Summary

To identify biomarkers, scientists first had to gain a solid understanding of both the genetic and behavioural effects of prenatal alcohol exposure (PAE). This project developed a neurobehavioural profile of rats throughout their life who had PAE in an attempt to characterize FASD-related behaviours better and eventually link those behaviours to genetic and epigenetic changes.

The power of using animal models is that everything—from alcohol dose to timing—is controlled, meaning any resulting phenotypic changes in the rat would directly correlate to its exposure to alcohol. As a result, researchers began to figure out how different variables were related to PAE.

From a behavioural standpoint, researchers identified several differences between PAE rats and controls, including delays in social recognition memory, fewer play initiations, and higher anxiety. PAE affected the expression of many genes and more than 200 biological processes, ranging from immune function to neurodevelopment.

The project also identified specific epigenetic changes in brain regions such as the hypothalamus and also in white blood cells that directly correlated to PAE. These discoveries may eventually lead to the identification of biomarkers not only of PAE, but also of developmental outcomes in the individual.

Result

This project found changes in stress hormone levels in rats as a result of PAE, so researchers decided to look at cortisol levels (the primary stress hormone in humans) in a cohort of children with FASD. They found these children had significantly higher evening cortisol concentrations than controls, a result that was especially evident in children who were living in conditions associated with low socioeconomic status. This work was another step towards a better characterization of FASD and the identification of potential biomarkers of PAE, and provides a clear example of how basic science can inform clinical care.

Team

Investigators

Joanne Weinberg, University of British Columbia
Michael Kobor, University of British Columbia
Carmen Rasmussen, University of Alberta

Collaborators

Gail Andrew, University of Alberta
Jacqueline Pei, University of Alberta
Kaitlyn McLachlan, University of Alberta