title: The enteric bacterial metabolite propionic acid alters brain and plasma phospholipid molecular species: further development of a rodent model of autism spectrum disorders.
abstract: Gastrointestinal symptoms and altered blood phospholipid profiles have been reported in patients with autism spectrum disorders (ASD). Most of the phospholipid analyses have been conducted on the fatty acid composition of isolated phospholipid classes following hydrolysis. A paucity of information exists on how the intact phospholipid molecular species are altered in ASD. We applied ESI/MS to determine how brain and blood intact phospholipid species were altered during the induction of ASD-like behaviors in rats following intraventricular infusions with the enteric bacterial metabolite propionic acid. Animals were infused daily for 8 days, locomotor activity assessed, and animals killed during the induced behaviors. Propionic acid infusions increased locomotor activity. Lipid analysis revealed treatment altered 21 brain and 30 blood phospholipid molecular species. 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. These alterations suggest that the propionic acid rat model is a useful tool to study aberrations in lipid metabolism known to affect membrane fluidity, peroxisomal function, gap junction coupling capacity, signaling, and neuroinflammation, all of which may be associated with the pathogenesis of ASD.
authors: The Kilee Patchell-Evans Autism Research Group, Department of Psychology, University of Western Ontario, London, ON, N6A 5C2, Canada. rthoma2@uwo.ca
authors: Raymond H
authors: RH
authors: Thomas
authors: Melissa M
authors: MM
authors: Meeking
authors: Jennifer R
authors: JR
authors: Mepham
authors: Lisa
authors: L
authors: Tichenoff
authors: Fred
authors: F
authors: Possmayer
authors: Suya
authors: S
authors: Liu
authors: Derrick F
authors: DF
authors: MacFabe
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002659:Child Development Disorders, Pervasive / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D002675:Child, Preschool; D004195:Disease Models, Animal; D004755:Enterobacteriaceae / Q000378:metabolism; D006801:Humans; D057967:Infusions, Intraventricular; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010743:Phospholipids / Q000097:blood*; D011422:Propionates / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D015415:Biomarkers; D010743:Phospholipids; D011422:Propionates; C029658:propionic acid