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The enteric bacterial metabolite propionic acid alters brain and plasma phospholipid molecular species: further development of a rodent model of autism spectrum disorders.

Thomas RH, Meeking MM, Mepham JR, Tichenoff L, Possmayer F, Liu S, MacFabe DF - J Neuroinflammation (2012)

Bottom Line: Propionic acid infusions increased locomotor activity.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Kilee Patchell-Evans Autism Research Group, Department of Psychology, University of Western Ontario, London, ON, N6A 5C2, Canada. rthoma2@uwo.ca

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.

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Positive ion mass spectra of brain lipid extract. ( A) Full ion scan of all lipids present in positive ion mode. ( B) Detection of [M + H]+ ions of PC and SM molecular species by precursor scanning of m/z 184. IS, internal standard; PC, phosphatidylcholine; SM, sphingomyelin.
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Figure 2: Positive ion mass spectra of brain lipid extract. ( A) Full ion scan of all lipids present in positive ion mode. ( B) Detection of [M + H]+ ions of PC and SM molecular species by precursor scanning of m/z 184. IS, internal standard; PC, phosphatidylcholine; SM, sphingomyelin.

Mentions: Behavioral assessment indicated animals developed abnormal (ASD-like) behaviors following PPA infusion (Figure 1). Animals were killed during the expression of these abnormal behaviors on day 8 and the molecular species of five phospholipid classes (SM, PC, PI, PS, and PE) were evaluated to determine whether they were altered during the expression of these behaviors. Phosphatidylcholine and SM molecular species were detected in the positive ion mode (Figure 2), while PI, PS, and PE molecular species were detected in the negative ion mode (Figure 3). Although the same molecular species for each phospholipid class were detected in control and PPA-infused animals, the analyses revealed a quantitative change in these lipid constituents following PPA infusions (Table 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10).


The enteric bacterial metabolite propionic acid alters brain and plasma phospholipid molecular species: further development of a rodent model of autism spectrum disorders.

Thomas RH, Meeking MM, Mepham JR, Tichenoff L, Possmayer F, Liu S, MacFabe DF - J Neuroinflammation (2012)

Positive ion mass spectra of brain lipid extract. ( A) Full ion scan of all lipids present in positive ion mode. ( B) Detection of [M + H]+ ions of PC and SM molecular species by precursor scanning of m/z 184. IS, internal standard; PC, phosphatidylcholine; SM, sphingomyelin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472254&req=5

Figure 2: Positive ion mass spectra of brain lipid extract. ( A) Full ion scan of all lipids present in positive ion mode. ( B) Detection of [M + H]+ ions of PC and SM molecular species by precursor scanning of m/z 184. IS, internal standard; PC, phosphatidylcholine; SM, sphingomyelin.
Mentions: Behavioral assessment indicated animals developed abnormal (ASD-like) behaviors following PPA infusion (Figure 1). Animals were killed during the expression of these abnormal behaviors on day 8 and the molecular species of five phospholipid classes (SM, PC, PI, PS, and PE) were evaluated to determine whether they were altered during the expression of these behaviors. Phosphatidylcholine and SM molecular species were detected in the positive ion mode (Figure 2), while PI, PS, and PE molecular species were detected in the negative ion mode (Figure 3). Although the same molecular species for each phospholipid class were detected in control and PPA-infused animals, the analyses revealed a quantitative change in these lipid constituents following PPA infusions (Table 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10).

Bottom Line: Propionic acid infusions increased locomotor activity.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Kilee Patchell-Evans Autism Research Group, Department of Psychology, University of Western Ontario, London, ON, N6A 5C2, Canada. rthoma2@uwo.ca

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.

Show MeSH
Related in: MedlinePlus