Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Biology

Supervisor

DR. SHIVA SINGH

Abstract

Maternal alcohol consumption during pregnancy results in a spectrum of behavioural and cognitive deficits collectively known as Fetal Alcohol Spectrum Disorders (FASD). Currently, little is know about if and how the external environment may modulate these deficits. I have used C57BL/6 mice to study this interaction between prenatal alcohol exposure and the postnatal environment. Alcohol exposure during synaptogenesis produces high levels of anxiety-like traits and decreased memory performance. Alcohol-exposed mice (and matched unexposed controls) were put in 'environmentally-enriched' conditions of voluntary exercise, physical activities and cognitive stimulation to ascertain the effects of a positive postnatal environment. The results show that environmental enrichment ameliorates anxiety-like behaviour and memory deficits of alcohol-exposed mice. However this recovery is incomplete, indicative of the long-lasting, potentially permanent damage of prenatal alcohol exposure on the developing brain.

In follow-up studies, I have uncovered gene expression changes in the hippocampus that are associated with behavioural and cognitive amelioration. To accomplish this, I have used mouse hippocampal RNA for microarray and RNA-Seq. My results have identified several key genes and molecular pathways that are associated with synaptic and structural plasticity, neurogenesis, long-term potentiation and angiogenesis. The behavioural and molecular results of this project represent a novel finding in the field of FASD research. The genes and pathways uncovered provide a possible explanation to understand FASD. They are also potential targets when formulating behavioural and pharmacological rehabilitative therapies.