Down-regulation of Signaling Mediator in Related to Increased Ratio of Docosahexaenoic Acid/Arachidonic Acid in Individuals with Autism Spectrum Disorders

Kunio Yui^1, , George Imataka², Yohei Kawasaki³ and Tsutomu Yamada³

¹Research Institute of Pervasive Developmental Disorders, Ashiya University, Rokurokusocho, Ashiya, Hyogo, Japan

²Department of Pediatrics, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi, Japan

³Department of Drug Evaluation and Information, School of Pharmaceutical Science University of Shizuoka, Shizuoka, Japan

Cite this paper:
Kunio Yui, George Imataka, Yohei Kawasaki and Tsutomu Yamada. Down-regulation of Signaling Mediator in Related to Increased Ratio of Docosahexaenoic Acid/Arachidonic Acid in Individuals with Autism Spectrum Disorders. Journal of Translational Medicine and Developmental Disorders. 2015; 2(1):1-9. doi: 10.12691/jtmdd-2-1-1

Abstract

Background and aim: Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by abnormal social interactions, communication deficits and stereotyped or repetitive behaviors. Converging lines of research indicate that the altered composition of polyunsaturated fatty acids (PUFAs) may contribute to the pathophysiology of ASD. Methods: We examined the relationships between the plasma ratios of omega-3PUFs/arachidonic acid (AA), plasma levels of 21 fatty acid fractions, and biomarkers of AA-related signaling mediators (ceruloplasmin, transferrin and superoxide dismutase) with the behavioral symptoms of 32 individuals with ASD (mean age, 13.5 ± 4.3 years old) and 20 age- and gender-matched normal controls (mean age, 13.2 ± 5.4 years old). Behavioral symptoms were assessed using the Aberrant Behavior Checklists (ABC). Results: Plasma levels of EPA, DPA and DHA, and the plasma ratios of docosahesaenoic acid (DHA)/AA were significantly higher while plasma levels of AA, 5,8,11,14-eicosatetraenoic acid and Cp were significantly lower in the 32 individuals with ASD compared with the 20 normal controls. The ABC scores were significantly increased in the ASD group compared to those of the control group. Discussion and Conclusion: High plasma DHA/AA ratio related to the increased plasma DHA levels and reduced plasma AA level may down-regulate mediators of AA signaling, such as Cp. Additionally, as 5,8,11,14-eicosatetraenoic acid is an arachidonate metabolite, the reduced plasma AA revels might have a pathophysiological factor in the reduced plasma Cp levels. Subsequently, reduced Cp levels may reduce the protective capacity of the brain against damage, which may cause in the pathophysiology underlying behavioral symptoms observed in individuals with ASD.

Keywords:
signaling mediators ceruloplasmin competitive interaction arachidonic acid docosahexaenoic acid

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