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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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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 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.](/paper-figures/39ecd586e42a417590926361dcf94e67/the-enteric-bacterial-metabolite-propionic-acid-alters-brain-and-plasma-figure-2.jpg)
![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.](/paper-figures/748d73fb9eae4c7b966c643e0fcc87bf/the-enteric-bacterial-metabolite-propionic-acid-alters-brain-and-plasma-figure-3.jpg)
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“However, the accumulation of SCFAs, and specifically of propionate, has also been shown to have broad effects on the nervous system physiology, and it is associated to the pathogenesis of ASD [175,176].”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [175]
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Metadata
- 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
- Venue
- Journal of Neuroinflammation
- Published
- 2012-07-02
- Volume
- 9
- Issue
- 1
- Pages
- 153-153
- ISSN
- 1742-2094 (ISSN-L)
- 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
- 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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