| Abstract No.: | C-C3080 |
| Country: | Canada |
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| Title: | USE OF TIME-OF-FLIGHT SECONDARY ION MASS SPECTROSCOPY (TOF-SIMS) TO ANALYSE WHITE MATTER EDEMA, INCREASED OXIDATIVE STRESS, AND ALTERED LIPID PROFILES IN PROPIONIC ACID TREATED RAT BRAIN: IMPLICATIONS FOR AUTISM SPECTRUM DISORDERS |
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| Authors/Affiliations: | 1 Derrick MacFabe*; 1 Heng-Yong Nie; 1 James Francis; 1 Roy Taylor; 1 Lisa Tichenoff; 1 Klaus-Peter Ossenkopp; 1 Mary Walzak; 1 Wayne Chang; 1 Leo Lau;
1 University of Western Ontario, London, ON, Canada
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| Content: | Background: Altered neuroinflammatory, lipid and oxidative stress profiles are found in autism spectrum disorders (ASDs). Furthermore, gastroenterological, dietary, and immunological factors have been implicated in ASD symptomatology. Propionic acid (PPA), a short chain fatty acid, a product of enteric bacteria, and a food preservative, has widespread effects on the above factors and can elicit consistent brain and behavioural changes in rodents reminiscent of ASDs. Time-of Flight-Secondary Ion Mass Spectroscopy (ToF-SIMS) is a powerful imaging technique which we have used to examine widespread ASD related biochemical markers in brain.
Objectives: To examine the effects of chronic infusions of PPA on behaviour, ToF-SIMS molecular imaging, and traditional immunohistochemistry .
Materials and Methods: Adult rats received intraventricular infusions of PPA (500ug/ul, pH 7.5) or PBS vehicle twice daily for 7 treatment days. Immediately following the second daily microinfusion, animals were tested in an automated open field (Versamax) and a variety of locomotor activity variables were assessed for 30min. Animals were sacrificed and brain sections examined via ToF-SIM imaging, or examined for neuropathology, (innate neuroinflammatory markers).
Results: PPA infusions produced increased locomotor activity. ToF-SIMS analysis of brain tissue from PPA treated rats produced clear images of forebrain structures (neocortex , external capsule, thalamus, hippocampus) which were grossly similar to control brain. However, ToF-SIMS showed increased Na, Cl, and N derivatives in external capsule, consistent with extracellular edema and increased oxidative stress. PPA reduced signal intensity of cholesterol and phosphatidyl choline in white matter. Effects were more extensive than the innate neuroinflammatory changes(GFAP, CD68, IbA1).
Conclusions: PPA infusions produced behavioural, neuropathological and molecular imaging changes in rats reminiscent of ASDs. Findings are consistent with ASD as a white matter disorder of increased oxidative stress, innate neuroinflammation and altered lipid profiles. ToF-SIMs is a powerful technique for the examination of neurological disorders. Current findings offer further support for PPA in rodent model for ASDs, providing a plausible dietary/gut/CNS link to this disorder.
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