Nakamura Madoka, Nakagami Akiko, Nakagaki Keiko, Yasue Miyuki, Kawai Nobuyuki, Ichinohe Noritaka
Department of Cognitive and Psychological Sciences, Graduate School of Informatics, Nagoya University, Nagoya, Japan.
Laboratory for Ultrastructure Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Japan.
Front Behav Neurosci. 2022 Aug 11;16:943759. doi: 10.3389/fnbeh.2022.943759. eCollection 2022.
Individuals with autism spectrum disorder (ASD) are exposed to a variety of stressors owing to their behavioral traits. Cortisol is a hormone typically associated with stress, and its concentration and response to stress are higher in individuals with ASD than in controls. The mechanisms underlying cortisol dysregulation in ASD have been explored in rodents. Although rodent models have successfully replicated the major symptoms of autism (i.e., impaired vocal communication, social interaction deficits, and restricted/repetitive patterns of behavior), evidence suggests that the hypothalamic-pituitary-adrenal (HPA) axis system differs between rodents and primates. We developed an ASD model in the common marmoset (), a New World monkey, utilizing prenatal exposure to valproic acid (VPA). In this study, we collected the salivary cortisol levels in VPA-exposed and unexposed marmosets in the morning and afternoon. Our results revealed that both VPA-exposed and unexposed marmosets showed similar diurnal changes in cortisol levels, which were lower in the afternoon than in the morning. However, heightened cortisol levels were observed throughout the day in VPA-exposed marmosets. These results are consistent with those of ASD in humans. Our results suggest that VPA-exposed marmosets show similarities not only in their behavioral patterns and brain pathologies, which we have reported previously, but also in hormonal regulation, validating the usefulness of VPA-exposed marmosets also as a tool for ASD stress research.
患有自闭症谱系障碍（ASD）的个体因其行为特征而面临各种压力源。皮质醇是一种通常与压力相关的激素，ASD患者体内其浓度及对应激的反应高于对照组。在啮齿动物中已对ASD中皮质醇失调的潜在机制进行了探索。尽管啮齿动物模型已成功复制出自闭症的主要症状（即发声交流受损、社交互动缺陷以及行为受限/重复模式），但有证据表明啮齿动物和灵长类动物的下丘脑 - 垂体 - 肾上腺（HPA）轴系统存在差异。我们利用孕期暴露于丙戊酸（VPA），在新世界猴普通狨猴中建立了一个ASD模型。在本研究中，我们收集了暴露于VPA和未暴露于VPA的狨猴在上午和下午的唾液皮质醇水平。我们的结果显示，暴露于VPA和未暴露于VPA的狨猴的皮质醇水平均呈现出相似的昼夜变化，下午的水平低于上午。然而，在暴露于VPA的狨猴中，全天皮质醇水平均升高。这些结果与人类ASD的结果一致。我们的结果表明，暴露于VPA的狨猴不仅在行为模式和脑病理学方面（我们之前已报道过）表现出相似性，而且在激素调节方面也表现出相似性，这证实了暴露于VPA的狨猴作为ASD应激研究工具的有效性。
