Cited by 209Autism Spectrum Disorder ResearchGut microbiota and healthTryptophan and brain disorders

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Etiology of autistic features: the persisting neurotoxic effects of propionic acid

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El-Ansary, Afaf K, Bacha, Abir Ben, Kotb, Malak·2012·Journal of Neuroinflammation

DOI 10.1186/1742-2094-9-74PMC PMC3425128

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Abstract

BACKGROUND: Recent clinical observations suggest that certain gut and dietary factors may transiently worsen symptoms in autism. Propionic acid (PA) is a short chain fatty acid and an important intermediate of cellular metabolism. Although PA has several beneficial biological effects, its accumulation is neurotoxic. METHODS: Two groups of young Western albino male rats weighing about 45 to 60 grams (approximately 21 days old) were used in the present study. The first group consisted of oral buffered PA-treated rats that were given a neurotoxic dose of 250 mg/kg body weight/day for three days, n = eight; the second group of rats were given only phosphate buffered saline and used as a control. Biochemical parameters representing oxidative stress, energy metabolism, neuroinflammation, neurotransmission, and apoptosis were investigated in brain homogenates of both groups. RESULTS: Biochemical analyses of brain homogenates from PA-treated rats showed an increase in oxidative stress markers (for example, lipid peroxidation), coupled with a decrease in glutathione (GSH) and glutathione peroxidase (GPX) and catalase activities. Impaired energy metabolism was ascertained through the decrease of lactate dehydrogenase and activation of creatine kinase (CK). Elevated IL-6, TNFα, IFNγ and heat shock protein 70 (HSP70) confirmed the neuroinflammatory effect of PA. Moreover, elevation of caspase3 and DNA fragmentation proved the pro-apoptotic and neurotoxic effect of PA to rat pups CONCLUSION: By comparing the results obtained with those from animal models of autism or with clinical data on the biochemical profile of autistic patients, this study showed that the neurotoxicity of PA as an environmental factor could play a central role in the etiology of autistic biochemical features.

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Figure 1 Measure of PA-induced DNA damage by comet assay (A): Control group of rats, (B): PA treated group of rats.CC BY · PubMed Central

Figure 2 Pearson’s correlations of the most significant positive and negative correlated variables with best fit line curve.CC BY · PubMed Central

Figure 3 Pearson’s correlations of the most significant positive and negative correlated variables with best fit line curve.CC BY · PubMed Central

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Authors: El-Ansary, A. K., Bacha, A. B., & Kotb, M.
Affiliations: King Saud University (SA)
University of Cincinnati (US)
Corresponding author: El-Ansary, Afaf K
ORCID: El-Ansary, Afaf K
Venue: Journal of Neuroinflammation
Publisher: Springer Science and Business Media LLC
Published: 2012-04-24
Volume: 9
Issue: 1
Pages: 74-74
ISSN: 1742-2094 (ISSN-L)
DOI: 10.1186/1742-2094-9-74
PMC: PMC3425128
OpenAlex: W2061631433
Cited by: 209
References: 59
Citations by year: 2026: 5 · 2025: 14 · 2024: 13 · 2023: 22 · 2022: 25 · 2021: 19 · 2020: 20 · 2019: 15 · 2018: 19 · 2017: 7 · 2016: 13 · 2015: 9 · 2014: 14 · 2013: 11 · 2012: 3
FWCI: 6.07
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, cc-by-sa)
Funders: King Saud University
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords: autism spectrum disorder, propionic acid, neurotoxicity, short-chain fatty acids, oxidative stress, lipid peroxidation, glutathione, neuroinflammation, apoptosis, caspase-3, energy metabolism, gut dysbiosis, dietary factors, animal models of autism
MeSH terms: Animals, Autistic Disorder, Brain, Disease Models, Animal, Male, Propionates, Random Allocation, Oxidative Stress, Rats

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Etiology of autistic features: the persisting neurotoxic effects of propionic acid

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