Saturday, May 22, 2010
Franklin Hall B Level 4 (Philadelphia Marriott Downtown)
9:00 AM
R. H. Thomas
,
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. A. Foley
,
The Kilee Patchell-Evans Autism Research Group, Departments of Psychology/Psychiatry, Division of Developmental Disabilities, University of Western Ontario, London, ON, Canada
J. Mepham
,
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
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: Phospholipids are major structural components of cell membranes and are critical in modulating membrane fluidity, cell signaling and mitochondrial function throughout neurodevelopment. Altered phospholipid and acylcarnitine profiles, suggestive of impaired peroxisomal and mitochondrial fatty acid metabolism, have been found in many patients with autism spectrum disorders (ASD). Propionic acid (PPA) a dietary short chain fatty acid, a metabolic intermediate of fatty acid metabolism, an end product of enteric bacterial fermentation, and a common food preservative have been implicated as a potential environmental trigger in ASD. PPA and other enteric short chain fatty acids (butyrate and acetate), affect diverse physiological processes such as cell signaling, immune function, gene expression, mitochondrial function and lipid metabolism, making these compounds plausible environmental triggers for the disorder. Intraventricular infusions of PPA can produce brain and behavioural changes similar to those seen in humans suffering from ASD
Objectives: We used the PPA rodent model to investigate if there are any evidence for abnormal brain lipid metabolism associated with the occurrence of autistic-like behavioral changes following intraventricular infusions of phosphate buffer saline (PBS), propionic (PPA) and butyric acids (BUT).
Methods: Infusions (0.26M, 4µL animal-1) was done twice daily for 7 days after which animals were sacrificed and brains lipids analyzed using thin layer chromatography (TLC) and gas chromatography-mass spectrometry and flame ionization detection (GC-MS/FID).Brain phospholipids were separated into SM, CL, PS+PI, PC and PE following TLC analysis.
Results: Hydrolysis of the separated phospholipid components revealed significant quantitative changes in fatty acid components after treatments with PPA and BUT compared to the controls (PBS), with PPA generally more extensive than BUT in altering the lipid composition. PPA infusion resulted in decreased levels of total monounsaturates, total ω6 fatty acids and elevated levels of total saturates in all the separated phospholipid species. In addition, a decline in total plasmalogen PE and the ratio of ω6: ω3 was also present. Conversely, there was a consistent significant (P = 0.02) increase in total acylcarnitines, total long chain (C12 to C24) acylcarnitines, total short chain (C2 to C9) acylcarnitines, and the ratio of free to bound carnitine following infusions with PPA and BUT. Increases in the accumulation of the following acylcarnitines: C2:0, C14:1, C15:0, C16:0, C16:1, C18:0, C18:1, C22:0, C22:1 and C24:0 accounted for the increase levels of total acylcarnitines observed following infusions with PPA and BUT.
Conclusions: These results provide evidence of a relationship between changes in brain lipid profiles and the occurrence of behavioral changes associated with autism spectrum disorder using the autism rodent model.
