Saturday, May 17, 2008
Champagne Terrace/Bordeaux (Novotel London West)
K. A. Foley
,
The Kilee Patchell-Evans Autism Research Group, Departments of Psychology/Psychiatry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
M. M. Gordon
,
The Kilee Patchell-Evans Autism Research Group, Departments of Psychology/Psychiatry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
A. R. Taylor
,
The Kilee Patchell-Evans Autism Research Group, Departments of Psychology/Psychiatry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
F. Boon
,
The Kilee Patchell-Evans Autism Research Group, Departments of Psychology/Psychiatry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
L. J. Tichenoff
,
The Kilee Patchell-Evans Autism Research Group, Departments of Psychology/Psychiatry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
K. -. P. Ossenkopp
,
The Kilee Patchell-Evans Autism Research Group, Departments of Psychology/Psychiatry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
D. F. MacFabe
,
The Kilee Patchell-Evans Autism Research Group, Departments of Psychology/Psychiatry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
Background: Dietary and gastrointestinal system influences may contribute to the manifestation of behaviors seen in autism spectrum disorders (ASDs). Neuroinflammatory changes, alterations in fatty acid metabolism, and blood brain barrier (BBB) permeability may be involved in the pathophysiology of ASDs. Propionic acid (PPA) is a short chain fatty acid, a by-product of enteric bacteria, and a food preservative that enters systemic circulation and the CNS by passive and active transport. We have found that PPA in rats produces behavioral and brain changes similar to that seen in ASD patients.
Objectives: Compare behavioral and neuropathological effects of spaced and chronic intraventricular PPA infusions in rodents.
Methods: Male adult Long-Evans rats received intraventricular infusions of buffered PPA (0.26 M, pH 7.5, 4 mL/infusion) or 0.1 M phosphate buffered saline (PBS) vehicle. Frequency of infusions varied from twice daily/7 days to once weekly/5 weeks. Immediately following microinfusion, animals were individually placed into an automated open-field for 30 min and locomotor activity was measured. 24h after last infusion, animals were perfused and brains examined immunohistochemically for markers of innate neuroinflammation, BBB permeability, and fatty acid transport.
Results: PPA treated animals displayed significant increases in locomotor activity and repetitive behavior compared to controls. Weekly PPA treated animals were significantly greater than daily treated PPA animals. Preliminary data suggest increased innate neuroinflammation (GFAP, CD68, Iba1, IL-6), BBB permeability (rat IgG), and monocarboxylate transporter-1 immunoreactivity in the white matter of weekly PPA animals than daily PPA animals.
Conclusions: PPA administration in rats increases locomotor activity and induces neuroinflammatory processes in the hippocampus and white matter that may model human ASDs. It appears that spaced (weekly) treatment may exacerbate PPA’s effects compared to chronic (daily) treatment. Recurrent PPA administration may mimic recurrent infections of PPA producing gut bacteria, offering further support for the PPA rodent model of ASDs.
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