Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba 305-8506, Japan.
Division of Life Science, Graduate School of Science and Engineering, Saitama University, Saitama City 338-8570, Japan.
Int J Mol Sci. 2021 Jan 7;22(2):538. doi: 10.3390/ijms22020538.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social communication, poor social interactions, and repetitive behaviors. We aimed to examine autism-like behaviors and related gene expressions in rats exposed to diesel exhaust (DE)-origin secondary organic aerosol (DE-SOA) perinatally. Sprague-Dawley pregnant rats were exposed to clean air (control), DE, and DE-SOA in the exposure chamber from gestational day 14 to postnatal day 21. Behavioral phenotypes of ASD were investigated in 10~13-week-old offspring using a three-chambered social behavior test, social dominance tube test, and marble burying test. Prefrontal cortex was collected to examine molecular analyses including neurological and immunological markers and glutamate concentration, using RT-PCR and ELISA methods. DE-SOA-exposed male and female rats showed poor sociability and social novelty preference, socially dominant behavior, and increased repetitive behavior. Serotonin receptor (5-HT(5B)) and brain-derived neurotrophic factor (BDNF) mRNAs were downregulated whereas interleukin 1 β (IL-β) and heme oxygenase 1 (HO-1) mRNAs were upregulated in the prefrontal cortex of male and female rats exposed to DE-SOA. Glutamate concentration was also increased significantly in DE-SOA-exposed male and female rats. Our results indicate that perinatal exposure to DE-SOA may induce autism-like behavior by modulating molecules such as neurological and immunological markers in rats.
自闭症谱系障碍(ASD)是一种神经发育障碍,其特征是社交沟通受损、社交互动不良和重复行为。我们旨在研究围产期接触柴油废气(DE)衍生二次有机气溶胶(DE-SOA)的大鼠是否存在类似自闭症的行为和相关基因表达。从妊娠第 14 天到产后第 21 天,将怀孕的 Sprague-Dawley 大鼠暴露于清洁空气(对照)、DE 和 DE-SOA 中。在 10~13 周龄的后代中,使用三腔社交行为测试、社交优势管测试和大理石掩埋测试来研究 ASD 的行为表型。通过 RT-PCR 和 ELISA 方法,收集前额叶皮质以检查包括神经和免疫标志物以及谷氨酸浓度在内的分子分析。DE-SOA 暴露的雄性和雌性大鼠表现出社交能力差和社会新颖性偏好降低、社会优势行为和重复行为增加。暴露于 DE-SOA 的雄性和雌性大鼠的 5-羟色胺受体(5-HT(5B))和脑源性神经营养因子(BDNF)mRNA 下调,而白细胞介素 1β(IL-β)和血红素加氧酶 1(HO-1)mRNA 上调。DE-SOA 暴露的雄性和雌性大鼠的谷氨酸浓度也显著增加。我们的结果表明,围产期接触 DE-SOA 可能通过调节神经和免疫标志物等分子在大鼠中诱导类似自闭症的行为。