Effects of the enteric bacterial metabolic product propionic acid on object-directed behavior, social behavior, cognition, and neuroinflammation in adolescent rats: Relevance to autism spectrum disorder
Abstract
Recent evidence suggests that a variety of environmental factors, including dietary and gastrointestinal agents, may contribute to autism spectrum disorders (ASD). Here we administered propionic acid (PPA), a short chain fatty acid that is used as a food preservative and also is a metabolic end-product of enteric bacteria in the gut, to adolescent (41 ± 4 days) male rats in a study of restricted/repetitive behavior, social behavior, and cognition. The goal was to further evaluate the effects of PPA in young rodents. PPA (4 μl of 0.26 M solution) was administered intracerebroventricularly prior to each behavioral test. Rats treated with PPA displayed restricted behavioral interest to a specific object among a group of objects, impaired social behavior, and impaired reversal in a T-maze task compared to controls given phosphate buffered saline. Immunohistochemical analysis of brain tissue from PPA rats revealed reactive astrogliosis and activated microglia, indicating an innate neuroinflammatory response. These findings are consistent with our earlier findings of ASD-relevant behavioral and brain events in adult rats given PPA, and support further study of effects of PPA in young rodents by establishing similar effects in adolescent animals.
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Intraventricular infusions of propionate result in increased repetitive behaviors, impaired sociability, epileptic and convulsive responses and are therefore used as a reliable model of autism spectrum disorder.
“In addition, intraventricular infusions of propionate result in increased repetitive behaviors, impaired sociability, epileptic and convulsive responses and is therefore used a reliable model of autism spectrum disorder (MacFabe et al., 2007;MacFabe et al., 2011).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as MacFabe et al., 2011
Some short-chain fatty acids such as propionic acid can be neurotoxic in higher concentrations and have been shown to cause behavioral abnormalities in rodent models.
“some SCFAs such as propionic acid (PPA) can be neurotoxic in higher concentrations and have been shown to cause behavioral abnormalities in rodent models [100, 101]”
From The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders (2018) · cites this paper as [101]
Bacteroides is an abundant genus at all ages, from infants to adults.
“Indeed, Bacteroides is an abundant genus at all ages, from infants to adults46.”
From Altered composition and function of intestinal microbiota in autism spectrum disorders: A systematic review (2019) · cites this paper as [46]
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- Authors
- MacFabe, D. F., Cain, N. E., Boon, F., Ossenkopp, K.-P., & Cain, D. P.
- Affiliations
- Western University (CA)
- Corresponding author
- Cain, Donald P.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 217
- Issue
- 1
- Pages
- 47-54
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W2153537282
- Semantic Scholar
- 483622c2bec9327289b4cf349d49896d9f2f9698
- Cited by
- 365
- References
- 67
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 10 · 2023: 30 · 2022: 22 · 2021: 41 · 2020: 36 · 2019: 30 · 2018: 30 · 2017: 21 · 2016: 32 · 2015: 20 · 2014: 22 · 2013: 22 · 2012: 18
- FWCI
- 8.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Sciences and Engineering Research Council of Canada
- 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 › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- propionic acid, autism spectrum disorder, short-chain fatty acids, gut microbiota, enteric bacteria, restricted and repetitive behaviors, social behavior, reversal learning, neuroinflammation, astrocyte activation, microglial activation, adolescent rats, intracerebroventricular administration, environmental risk factors
- MeSH terms
- Animals, Astrocytes, Child, Child Development Disorders, Pervasive, Cognition, Disease Models, Animal, Exploratory Behavior, Fatty Acids, Volatile, Hippocampus, Humans, Inflammation, Injections, Intraventricular, Propionates, Social Behavior, Microglia, Maze Learning, Rats, Long-Evans, Rats
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