Decreased Expression of EP3 Receptor mRNA in the Brain of Mouse Model of Autism Spectrum Disorder.

Kusnandar Anggadiredja, Neng Fisheri Kurniati, Atsushi Kasai, Hitoshi Hashimoto
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Abstract

Background: Accumulating evidence has implicated the role of neuroinflammation in the pathology of autism spectrum disorder (ASD), a neurodevelopmental disorder.

Objectives: To investigate the expression of prostaglandin EP3 (EP3) receptor mRNA in the brain of ASD mouse model.

Methods: Pregnant mice were injected with valproic acid (VPA) 500 mg/kg intraperitoneally at 12.5 d gestation. The offspring were tested at the age of 5-6 weeks old for their social interaction behavior. Each mouse was assessed for prostaglandin EP3 receptor expression in the prefrontal cortical, hippocampal and cerebellar areas one day after the behavioral test.

Results: Compared to the naive, mice born to dams treated with VPA demonstrated a significantly shorter duration of sniffing behavior, a model of social interaction. Results further showed that the expression of EP3 receptor mRNA was significantly lower in all three brain regions of the mice born to VPA-treated dams.

Conclusion: The present study provides further evidence of the relevance of the arachidonic acid cascade as an essential part of neuroinflammation in the pathology of ASD.

自闭症谱系障碍小鼠模型中EP3受体mRNA的表达降低。
背景:越来越多的证据表明神经炎症在自闭症谱系障碍(ASD)病理中的作用,ASD是一种神经发育障碍。目的:探讨前列腺素EP3 (EP3)受体mRNA在ASD小鼠模型脑组织中的表达。方法:妊娠12.5 d时,腹腔注射丙戊酸(VPA) 500 mg/kg。这些幼崽在5-6周大时接受社会互动行为测试。每只小鼠在行为测试后1天评估前额皮质、海马和小脑区域前列腺素EP3受体的表达。结果:与幼鼠相比,经VPA治疗的母鼠的嗅探行为持续时间明显缩短,这是一种社会互动模式。结果进一步表明,在vpa处理的小鼠出生的所有三个脑区中,EP3受体mRNA的表达均显著降低。结论:本研究进一步证明花生四烯酸级联反应是ASD病理中神经炎症的重要组成部分。
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