Down-regulation of a signaling mediator in association with lowered plasma arachidonic acid levels in individuals with autism spectrum disorders

摘要

Previous studies have indicated that the altered composition of polyunsaturated fatty acids (PUFAs) might contribute to the pathophysiology of autism spectrum disorder (ASD). We examined the relationship between the plasma fatty acid levels, expressed as mu g/ml, and the plasma levels of biomarkers of AA-related signaling mediators, such as ceruloplasmin, transferrin and superoxide dismutase, and assessed the behavioral symptoms of 30 individuals with ASD (mean age, 13.6 +/- 4.3 years old) compared with 20 age- and gender-matched normal controls (mean age, 13.2 +/- 5.4 years old) using Aberrant Behavior Checklists (ABC). The plasma levels of EPA and the plasma ratios of EPA/AA were significantly higher, while the plasma levels of AA and metabolites, such as 5,8,11,14-eicosatetraenoic acid, adrenic acid, and ceruloplasmin (Cp), were significantly lower in the 30 individuals with ASD compared with the 20 normal controls. The ABC scores were significantly increased in the ASD group compared with those of the control group. Thus, the results of the present study revealed that reduced plasma levels of AA and metabolites in association with high plasma EPA/AA ratios might down-regulate AA-related signaling mediators, such as Cp. Subsequently, reduced plasma Cp levels might reduce the protective capacity for brain damage, resulting in the pathophysiology underlying the behavioral symptoms in individuals with ASD. These findings suggest that reduced plasma AA levels may downregulate Cp. (C) 2015 Published by Elsevier Ireland Ltd.