Modulation of Omega-6 Polyunsaturated Fatty Acid-dependent Signaling and its Therapeutic Potential for the Core Symptoms in Individuals with Autism Spectrum Disorders

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  • Yui Kunio
    Department of Drug Evaluation and Informatics, School of Pharmaceutical Science, University of Shizuoka Department of Pediatrics, Dokkyo Medical University Research Institute of Pervasive developmental Disorders, Ashiya University Graduate School of Education
  • Kawasaki Yohei
    Department of Pediatrics, Dokkyo Medical University
  • Yamada Hiroshi
    Department of Pediatrics, Dokkyo Medical University

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  • オメガ-6 脂肪酸アラキドン酸のシグナリング調整と自閉症スペクトラム障害の中核症状の改善
  • オメガ-6 シボウサン アラキドンサン ノ シグナリング チョウセイ ト ジヘイショウ スペクトラム ショウガイ ノ チュウカク ショウジョウ ノ カイゼン

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Abstract

We examined the relationships between plasma levels of fatty acids and biomarkers of AA-related signaling mediators (ceruloplasmin, transferrin and superoxide dismutase) with the behavioral and social symptoms of 21 individuals with ASD (mean age, 13.1 ± 4.5 years old) and 21 age-and gender-matched normal controls (mean age, 13.9 ± 5.7 years old). Behavioral and social symptoms were assessed using the Aberrant Behavior Checklists (ABC) and Social Responsiveness Scale (SRS) respectively. To compensate reduced plasma AA levels, the 21 individuals with ASD were treated with supplementation (precursor of omega-6 PUFAS, linoleic acid 480 mg/day plus omega-3 PUFA precursor α-linoleinic acid 240mg/day) for 16 weeks. Plasma EPA levels and arachidic acid, and the plasma ratios of eicosapentaenoic acid (EPA) /AA and docosahesaenoic acid (DHA) /AA were significantly higher while plasma levels of AA and ceruloplasmin (Cp) were significantly lower in the 21 individuals with ASD compared with the 21 controls. The ABC and SRS scores were significantly increased in the ASD group than in the control group. The 16-week treatment with AA supplementation significantly improved the four subscale scores ant total scores. In conclusion, this study firstly revealed that the reduced plasma levels of AA in association with high plasma EPA/AA ratio may down- regulate AA- related signaling mediator such as Cp. Thelowered Cp levels may reduce the protective capacity for the brain damage, causing in the pathophysiology underlying the core symptoms of individuals with ASD. Supplementation with higher doses of omega-6 fatty acid has therapeutic potential for the core ASD symptoms.

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