Date of Award

2011

Degree Type

Thesis

Degree Name

Master of Science

Program

Neuroscience

Supervisor

Derrick MacFabe

Second Advisor

Peter Ossenkopp

Abstract

Dietary and gastrointestinal factors may be associated with the development/worsening of autistic symptoms in a subset of patients. Propionic acid (PPA) is a metabolic byproduct of gut bacterial fermentation.

Intracerebroventricular (ICV) infusions of PPA in rodents produce transient behavioural and biochemical changes similar to those seen in autism. The permanence of the cognitive deficits associated with the PPA rodent model of autism was assessed using adult male rats in the Morris water maze (MWM).

Following an ICV regimen of PPA or vehicle (2x/day, 7 days), rats were tested in the MWM (acquisition) and then one week later for reversal. On reversal day,perseveratory behaviours were assessed following 2 additional infusions. PPA-S treated rats displayed longer search latencies to find the platform during MWM acquisition, but showed normal reversal one week later. A second experiment used nonspatial pretraining prior to treatment in order to differentiate between spatial versus strategy deficits, and effects of stress in the MWM. Similar to the first study, rats treated with PPA on reversal day showed impairments in the maze, regardless ofinitial drug treatment. In summary, PPAtreatment caused impairments in cognition as measured in the MWM, but these behavioural impairments appear to return to baseline after the drug treatment is stopped, suggesting that some effects of PPA may be reversible.

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