Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Neuroscience

Supervisor

Dr. Klaus-Peter Ossenkopp

2nd Supervisor

Dr. Martin Kavaliers

Joint Supervisor

Abstract

Dietary and gastrointestinal factors may contribute to the etiology of autism spectrum disorders (ASD). Propionic acid (PPA) is a short chain fatty acid that is an intermediary of fatty acid metabolism and a fermentation by-product of enteric bacteria. Using a single infusion (Chapter 2) and repeated infusions (Chapter 3), the temporal relationship between PPA-induced locomotor activity and astrocyte/microglial changes was demonstrated. Adult Long-Evans rats were centrally infused with 4µl of 0.26M PPA or 0.1M PBS vehicle once or once a week for four weeks. Locomotor activity was evaluated for 20 minutes following infusion and again several days later to assess drug-free activity. Rats were perfused at various time-points post-final infusion, and brain tissue was immunohistochemically (GFAP, CD68) analyzed. PPA produced rapid increases in locomotor activity and later, pronounced changes in glial cell activation. PPA’s effects on neurotransmitters, calcium signaling, mitochondrial metabolism, and immune functioning are likely underlying mechanisms.


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