Altered brain phospholipid and acylcarnitine profiles in propionic acid infused rodents: further development of a potential model of autism spectrum disorders.
Recent studies have demonstrated intraventricular infusions of propionic acid (PPA) a dietary and enteric short-chain fatty acid can produce brain and behavioral changes similar to those observed in autism spectrum disorder (ASD). The effects of PPA were further evaluated to determine if there are any alterations in brain lipids associated with the ASD-like behavioral changes observed following intermittent intraventricular infusions of PPA, the related enteric metabolite butyric acid (BUT) or phosphate-buffered saline vehicle. Both PPA and BUT produced significant increases (p < 0.001) in locomotor activity (total distance travelled and stereotypy). PPA and to a lesser extent BUT infusions decreased the levels of total monounsaturates, total omega6 fatty acids, total phosphatidylethanolamine plasmalogens, the ratio of omega6 : omega3 and elevated the levels of total saturates in separated phospholipid species. In addition, total acylcarnitines, total longchain (C12-C24) acylcarnitines, total short-chain (C2 to C9) acylcarnitines, and the ratio of bound to free carnitine were increased following infusions with PPA and BUT. These results provide evidence of a relationship between changes in brain lipid profiles and the occurrence of ASD-like behaviors using the autism rodent model. We propose that altered brain fatty acid metabolism may contribute to ASD.
Thomas
Raymond H
RH
The Kilee Patchell-Evans Autism Research Group, Department of Psychology and Biology, University of Western Ontario, London, Ontario, Canada.
Foley
Kelly A
KA
Mepham
Jennifer R
JR
Tichenoff
Lisa J
LJ
Possmayer
Fred
F
MacFabe
Derrick F
DF
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000378:metabolism; D002648:Child; D002659:Child Development Disorders, Pervasive; D002855:Chromatography, Thin Layer / Q000379:methods; D004195:Disease Models, Animal; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010743:Phospholipids / Q000378:metabolism*; D011422:Propionates / Q000008:administration & dosage*; D051381:Rats; D020318:Rats, Long-Evans; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology
D010743:Phospholipids; D011422:Propionates; C116917:acylcarnitine; C029658:propionic acid; D002331:Carnitine