| Abstract No.: | C-D3125 |
| Country: | Canada |
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| Title: | INCREASED LOCOMOTOR ACTIVITY, NEUROINFLAMMATION, AND MONOCARBOXYLATE TRANSPORTER IMMUNOREACTIVITY FOLLOWING INTRAVENTRICULAR INFUSIONS OF PROPIONIC ACID IN RATS: SPACED VS CHRONIC ADMINISTRATION |
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| Authors/Affiliations: | 1 Kelly Foley*; 1 Melissa Gordon; 1 Roy Taylor; 1 Francis Boon; 1 Lisa Tichenoff; 1 Klaus-Peter Ossenkopp; 1 Derrick MacFabe;
1 University of Western Ontario, London, ON, Canada
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| Content: | 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 changes in 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 those seen in ASD patients.
Objective: To compare behavioral and neuropathological effects of spaced and chronic intraventricular PPA infusions in rodents.
Materials and Methods: Male adult Long-Evans rats received intraventricular infusions of buffered PPA (0.26 M, pH 7.5, 4 L/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 tested in a non-novel automated open-field for 30 min and locomotor activity was measured. 24h after the 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 behaviors compared to controls. Animals given weekly PPA treatments showed greater hyperactivity 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 treated PPA animals relative to daily PPA treated animals.
Conclusions: PPA administration in rats increases locomotor activity and induces neuroinflammatory processes in the hippocampus and white matter that may model human ASDs. Spaced (weekly) treatments may exacerbate PPA’s effects compared to chronic (daily) treatments. 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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