Cited by 200Autism Spectrum Disorder ResearchMetabolomics and Mass Spectrometry StudiesFatty Acid Research and Health

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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

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Thomas, Raymond H, Meeking, Melissa M, Mepham, Jennifer R, Tichenoff, Lisa, Possmayer, Fred, Liu, Suya, MacFabe, Derrick F·2012·Journal of Neuroinflammation

DOI 10.1186/1742-2094-9-153PMC PMC3472254

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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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Figure 1 Number of horizontal movements (A), number of vertical movements (B), counterclockwise revolutions (C), clockwise revolutions (D), number of stereotypic movements (E), horizontal movement time (F), and total distance travelled (G), representing abnormal animal behavior following ICV infusions with PPA and PBS. Animals received ICV infusions of PPA ( n = 12) and PBS ( n = 12) twice a day for 7 consecutive days. Behavioral measurements were monitored immediately after each infusion over 30 min. Values represent means ± SE over 7 days. Bars accompanied by asterisks indicate significant difference between treatments at LSD = 0.05, n = 12 per treatment group. PBS, phosphate buffered saline solution; PPA, propionic acid.CC BY · PubMed Central

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.CC BY · PubMed Central

Figure 3 Negative ion mass spectra of brain lipid extract. ( A) Detection of all [M-H] - ions of glycerophospholipids by precursor ion scan of m/z 153. ( B) Detection of PI molecular species by precursor ion scanning of m/z 241. ( C) Detection of PS molecular species by neutrol loss of 87 D. ( D) Detection of PE molecular species by precursor ion scanning of m/z 196. GPL, glycerophospholipids; IS, internal standard; PI, phosphatidylinositol; PS, phosphatidylserine; PE, phosphatidylethanolamine.CC BY · PubMed Central

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Authors: Thomas, R. H., Meeking, M. M., Mepham, J. R., Tichenoff, L., Possmayer, F., Liu, S., & MacFabe, D. F.
Affiliations: Western University (CA)
Corresponding author: Thomas, Raymond H
ORCID: Thomas, Raymond H
Possmayer, Fred
Liu, Suya
Venue: Journal of Neuroinflammation
Publisher: Springer Science and Business Media LLC
Published: 2012-07-02
Volume: 9
Issue: 1
Pages: 153-153
ISSN: 1742-2094 (ISSN-L)
DOI: 10.1186/1742-2094-9-153
PMC: PMC3472254
OpenAlex: W2103294794
Cited by: 200
References: 68
Citations by year: 2026: 9 · 2025: 9 · 2024: 6 · 2023: 10 · 2022: 17 · 2021: 22 · 2020: 19 · 2019: 17 · 2018: 17 · 2017: 10 · 2016: 22 · 2015: 15 · 2014: 11 · 2013: 12 · 2012: 4
FWCI: 6.88
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
www.creativecommons.org/licenses/by/2.0 (unspecified)
Locations: Journal of Neuroinflammation (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders: Autism Research Institute
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Keywords: autism spectrum disorder, propionic acid, gut-brain axis, phospholipid molecular species, brain phospholipids, plasma phospholipids, intraventricular infusion, locomotor activity, sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, plasmalogens, lipid metabolism, neuroinflammation, membrane fluidity
MeSH terms: Animals, Brain, Child Development Disorders, Pervasive, Child, Preschool, Disease Models, Animal, Enterobacteriaceae, Humans, Motor Activity, Phospholipids, Propionates, Biomarkers, Rats, Long-Evans, Rats, Infusions, Intraventricular

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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

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