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Saturday, May 17, 2008
Champagne Terrace/Bordeaux (Novotel London West)
Background: Altered neuroinflammatory, lipid and oxidative stress profiles are found in autism spectrum disorders (ASDs). Dietary, gastroenterological and immunological factors have been implicated in ASD symptomatology. Propionic acid (PPA) is a short chain fatty acid, a product of enteric bacteria, and a food preservative. PPA 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 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 .
Methods: Adult rats received intraventricular infusions of PPA (500ug/ul, pH 7.5) or PBS vehicle twice daily for 7 treatment days. Immediately following microinfusion, animals were individually placed into 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 neuropathologically (innate neuroinflammatory markers).
Results: PPA infusions produced increased locomotor activity. ToF-SIMS analysis of PPA treated rat brain revealed 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 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, inflammation and altered lipid profiles. ToF-SIMs is a powerful technique to examine neurological disorders. Findings offer further support for PPA in rodent model for ASDs, providing a plausible dietary/gut/CNS link to this disorder.
Objectives: To examine the effects of chronic infusions of PPA on behaviour, ToF-SIMS molecular imaging and traditional immunohistochemistry .
Methods: Adult rats received intraventricular infusions of PPA (500ug/ul, pH 7.5) or PBS vehicle twice daily for 7 treatment days. Immediately following microinfusion, animals were individually placed into 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 neuropathologically (innate neuroinflammatory markers).
Results: PPA infusions produced increased locomotor activity. ToF-SIMS analysis of PPA treated rat brain revealed 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 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, inflammation and altered lipid profiles. ToF-SIMs is a powerful technique to examine neurological disorders. Findings offer further support for PPA in rodent model for ASDs, providing a plausible dietary/gut/CNS link to this disorder.