Abstract

BackgroundFatty acids are essential dietary nutrients, and one of their important roles is providing polyunsaturated fatty acids (PUFAs) for the growth and function of nervous tissue. Short chain fatty acids (SCFAs) are a group of compounds derived from the host microbiome that were recently linked to effects on the gut, the brain, and behavior. They are therefore linked to neurodevelopmental disorders such as autism. Reduced levels of PUFAs are associated with impairments in cognitive and behavioral performance, which are particularly important during brain development. Recent studies suggest that omega -3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are involved in neurogenesis, neurotransmission, and protection from oxidative stress. Omega-3 PUFAs mediate some of these effects by antagonizing Omega-6 PUFA (arachidonic acid, AA)-induced proinflammatory prostaglandin E2; (PGE2) formation.MethodsIn this work, the absolute and relative concentrations of propionic (PPA), butyric and acetic acids, as well as PUFAs and their precursors (α-Linolenic and linoleic), were measured in the brain tissue of PPA-neurointoxicated rat pups (receiving 250 mg PPA/Kg body weight for 3 consecutive days) as a rodent model with persistent autistic features compared with healthy controls.ResultsThe data revealed remarkably lower levels of omega6/omega3, α-Linolenic/Linoleic, α-Linolenic/EPA, α-Linolenic/DHA, EPA/DHA, and AA/Linoleic acid ratios in PPA-intoxicated rats. The role of these impaired ratios is discussed in relation to the activity of desaturases and elongases, which are the two enzymatic groups involved in the synthesis of PUFAs from their precursors. The relationship between the abnormal relative concentrations of the studied fatty acids and oxidative stress, neurotransmission, and neuroinflammation is also discussed in detail.ConclusionsThis study demonstrates that fatty acid ratios are useful for understanding the mechanism of PPA neurotoxicity in a rodent model of autism. Therefore, it is possible to use these ratios for predictions in patients with this disorder.

Highlights

  • Lipids constitute nearly 60 percent of the brain’s structure

  • This work is an attempt to understand the mechanism of propionic acid (PPA) neurotoxicity by considering the impact of relatively impaired level SCFAs and polyunsaturated fatty acids (PUFAs) in PPAintoxicated rats compared with a healthy untreated control group; the results suggest that the ratio is more important than the quantity of individual fatty acids

  • Data representing the absolute and relative values of SCFAs and PUFAs are presented as the mean ± S.D for 6 independent experiments in Tables 1 and 2

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Summary

Introduction

Lipids constitute nearly 60 percent of the brain’s structure. Fatty acids are among the most important molecules that determine the brain’s integrity and ability to work efficiently. Essential fatty acids are important for brain development during both the fetal and postnatal period. Beyond their important role in building the brain’s structure, certain fatty acids act as messengers and are involved in the synthesis and function of neurotransmitters and the molecules of the immune system. Short chain fatty acids (SCFAs) are a group of compounds derived from the host microbiome that were recently linked to effects on the gut, the brain, and behavior. They are linked to neurodevelopmental disorders such as autism. Omega-3 PUFAs mediate some of these effects by antagonizing Omega-6 PUFA (arachidonic acid, AA)-induced proinflammatory prostaglandin E2 (PGE2) formation

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