Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Neuroscience

Supervisor

Peter Ossenkopp

2nd Supervisor

Dr. Martin Kavaliers

Joint Supervisor

Abstract

The gut microbiome plays an important role in immune functioning and neurodevelopment. Altered microbiome composition, leading to short chain fatty acid, and/or immune system dysfunction has been observed in children with autism spectrum disorders (ASD). This thesis describes the developmental influence of prenatal exposure to propionic acid (PPA), a metabolic fermentation product of enteric bacteria, or prenatal exposure to lipopolysaccharide (LPS), a bacterial mimetic and product of enteric bacteria, on a range of behaviours in male and female neonatal, adolescent and adult rats. Study one evaluated the effects of prenatal PPA and LPS, and postnatal PPA, on developmental milestones in early life and on subsequent locomotor activity and anxiety-related behaviours. Study two examined acoustic startle response (ASR) and prepulse inhibition, while the third examined social behaviours. Overall, prenatal and postnatal treatments subtly altered behaviour in a sex- and test-specific manner. Male and female rats showed developmental delay in the day of eye opening and in acquiring a nest seeking odor discrimination. Prenatal and postnatal PPA treatments increased anxiety-related behaviour and altered ASR. Male rats displayed alterations in social behaviour and locomotor activity that was not observed in female rats, supporting the male bias seen in autism. However, female rats also showed augmented sensitivity to PPA, displaying repetitive behaviour, altered ASR, and decreased prepulse inhibition, in agreement with the evidence that these behaviours are more severe in females with ASD. Together, these findings demonstrate that the metabolic products of enteric bacteria, PPA and LPS, may alter development in ways resembling ASD.

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