The Enteric Bacterial Metabolite Propionic Acid Alters Brain and Plasma Intact Phospholipid Molecular Species: Implications In Autism Spectrum Disorders

Thursday, May 17, 2012
Sheraton Hall (Sheraton Centre Toronto)
11:00 AM
R. H. Thomas1,2, M. M. Meeking3, J. Mepham1, L. J. Tichenoff1, F. Possmayer4 and D. F. MacFabe1,5,6, (1)The Kilee Patchell-Evans Autism Research Group, Dept. of Psychology, University of Western Ontario, London, ON, Canada, (2)Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada, (3)Psychology, University of Western Ontario, London, ON, Canada, (4)Obstetrics/Gynecology and Biochemistry,, University of Western Ontario, London, ON, Canada, (5)The Kilee Patchell-Evans Autism Research Group, University of Western Ontario, London, ON, Canada, (6)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 the major structural components of neuronal membranes and are essential for proper brain function and development. Several recent studies have reported the existence of altered phospholipid profiles in patients with autism spectrum disorders (ASD). However, most of the analyses in these studies were done following hydrolysis of the separated phospholipids which destroys their structures. Consequently, there is a paucity of information concerning how the intact phospholipid molecular species are altered in ASD in relation to behavioral manifestations.

Objectives:  

We used ESI/MS to determine how blood and brain intact phospholipid species were altered during the induction of ASD-like behaviors in rats following intraventricular infusions with the enteric bacterial metabolite propionic acid

Methods:  

Animals were infused twice daily for 8 days, locomotor activity assessed and animals sacrificed during the induced behaviours and brain and blood samples collected for phospholipid analyses. Phospholipids were analysed by ESI-MS operated in positive ion mode, using precursor ion scans specific for each phospholipid class.

Results:  

Brain and blood lipid analysis revealed propionic acid infusions increased (p ≤ 0.001) locomotor activity and altered 21brain and 30 blood phospholipid molecular species. Most notable alterations were observed in the composition of brain SM, diacyl mono and polyunsaturated PC, PI, PS, PE and plasmalogen PC and PE molecular species.

Conclusions:  

These alterations are suggestive that aberrations in lipid metabolism which are known to affect membrane fluidity, peroxisomal functions, gap junction coupling capacity, and signalling during neuroinflammation may be associated with the PPA induced ASD-like behaviours in the rodent model of ASD.

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