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.
Highlights
Autism spectrum disorders (ASD) are a family of disorders characterized by stereotypic and restrictive patterns of behavior, deficits in social interactions, and impairments in language development and communication skills [1]
Short chain fatty acids can concentrate intracellularly, in acidotic conditions [18,19], where they may have deleterious effects on brain development and function [13,20,21]. This could be important in the context of ASD, since propionic acid (PPA) is known to affect cell signaling [22], neurotransmitter synthesis and release [20], mitochondrial function/coenzyme A (CoA) sequestration [16], lipid metabolism [23] immune function [24], gap junction modulation [19], and gene expression [25], all of which have been implicated in ASD [7,25,26,27,28]
There was no significant difference in baseline behavior between animals assigned to the PPA and phosphate buffered saline (PBS) treatment groups
Summary
Autism spectrum disorders (ASD) are a family of disorders characterized by stereotypic and restrictive patterns of behavior, deficits in social interactions, and impairments in language development and communication skills [1]. If there are genetic and/or acquired aberrations in metabolism [7,16], higher than normal levels of short chain fatty acids can be present in the circulating blood, and can cross the gut-blood and blood brain barriers passively and/or actively via high affinity transporters [17]. Under these conditions, short chain fatty acids can concentrate intracellularly, in acidotic conditions [18,19], where they may have deleterious effects on brain development and function [13,20,21]. This could be important in the context of ASD, since PPA is known to affect cell signaling [22], neurotransmitter synthesis and release [20], mitochondrial function/CoA sequestration [16], lipid metabolism [23] immune function [24], gap junction modulation [19], and gene expression [25], all of which have been implicated in ASD [7,25,26,27,28]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
