The role of lipid peroxidation in individuals with autism spectrum disorders
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ORIGINAL ARTICLE
The role of lipid peroxidation in individuals with autism spectrum disorders Kunio Yui 1
&
George Imataka 2 & Hitomi Sasaki 1 & Ryoichi Shiroki 1
Received: 9 March 2020 / Accepted: 1 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The role of malondialdehyde-modified low-density lipoprotein (MDA-LDL), an oxidized LDL, in the pathophysiology of autism spectrum disorder (ASD) is unclear. We studied association between MDA-LDL and behavioral symptoms in 11 individuals with ASD and 7 age -matched normal controls. Behavioral symptoms were assessed using the Aberrant Behavior Checklists (ABC). Because small sample size in this study, three measures were conducted: first, employment of adaptive Lasso for enhancing the accuracy of prediction and interpretability; second, calculation of coefficient of variation for an appropriate selection of plasma variables; and third, selection of good candidates of plasma variables. Plasma levels of MDA-LDL, eicosapentaenoic acid, docosahexaenoic acid (DHA) and DHA/arachidonic acid ratios were significantly higher, while plasma superoxide dismutase (SOD) levels were significantly lower in the ASD group than in the control group. The total ABC scores were significantly higher in the ASD group than in the control group. Multiple linear regression analysis and the adaptive Lasso revealed association of increased plasma DHA levels with the ABC total scores and increased plasma MDA-LDL levels. Such association between DHA and plasma MDA-LDL levels may contribute to behavior in individuals with ASD. Keywords Lipid peroxidation . Autistic behavior . Malondialdehyde-modified low-density lipoprotein . Docosahexaenoic acid (DHA)
Introduction Studying the mechanisms of action of lipid peroxidation is an important research strategy to understand the pathophysiology of autism spectrum disorder (ASD) (Meguid et al. 2011). Membrane phospholipids in the brain are highly enriched in polyunsaturated fatty acids (PUFAs), which are converted to other products including reactive aldehydes such as lipid peroxidation: production. Of reference, two main omega-6 fatty acids lipid peroxidation products: malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE) have been reported (Ayala et al. 2014). MDA has been known as a useful biomarker for lipid peroxidation of omega-3 and omega-6 fatty acids (Ayala et al. 2014). However, which of n-3 or n-6 * Kunio Yui [email protected] 1
Department of Urology, Fujita Medical University School of Medicine, Aichi 470-1192, Japan
2
Department of Pediatrics, Dokkyo Medical University, Tochigi 321-0293, Japan
PUFAs mainly contributes to the formation of MDA is still under debate. A few studies have reported the elevation of plasma MDA in 20 children with ASD compared to agematched 20 controls (Meguid et al. 2011), and that blood MDA levels in 45 autistic children aged 3–11 years were higher than age-matched 42 normal controls (GonzálezFraguela et al. 2013). Accumulating evidence suggested a positive relationship
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