Psychiatric Ward, Qingdao Mental Health Center, Qingdao University, No 299 Nanjing Road, Qingdao, 266034 Shandong, China.
Department of Laboratory Medicine, Lao-shan Disease Area, the Affiliated Hospital of Qingdao University, Qingdao, 266000 Shandong, China.
ACS Chem Neurosci. 2020 Nov 18;11(22):3786-3792. doi: 10.1021/acschemneuro.0c00482. Epub 2020 Nov 9.
Autism spectrum disorder (ASD) is a severe neurological and developmental disorder that impairs a person's ability to socialize and communicate and affects behavior. The number of patients diagnosed with ASD has risen rapidly. However, the pathophysiology of ASD is poorly understood, and drugs for ASD treatment are strikingly limited. This study aims to evaluate the roles of glyoxalase 1 (GLO1)-methylglyoxal (MG)-γ-aminobutyric acid (GABA) signaling in ASD using a valproic acid (VPA)-induced animal model of autism. The GLO1 levels were analyzed by RT-qPCR and Western blot assay, and MG levels were measured with a Methylglyoxal Assay Kit. The open-field and sniff duration tests were used to assess the interest and anxiety of VPA mice. The three-chamber, marble-burying, and tail-flick tests were applied to determine the sociability, repetitive behavior, and nociceptive threshold of VPA mice. Our results demonstrated that increased GLO1 and decreased MG were observed in VPA mice. Administration of --bromobenzylglutathione cyclopentyl diester (BrBzGCp2), a GLO1 inhibitor, was beneficial for alleviating anxiety, reducing repetitive behavior, and improving the impaired sociability and nociceptive threshold of VPA mice. BrBzGCp2 treatment may be developed as a promising therapeutic strategy for patients with ASD.
自闭症谱系障碍（ASD）是一种严重的神经发育障碍，损害了患者的社交和沟通能力，并影响了行为。被诊断为 ASD 的患者数量迅速增加。然而，ASD 的病理生理学机制尚不清楚，治疗 ASD 的药物也极为有限。本研究旨在使用丙戊酸（VPA）诱导的自闭症动物模型评估乙二醛酶 1（GLO1）-甲基乙二醛（MG）-γ-氨基丁酸（GABA）信号在 ASD 中的作用。通过 RT-qPCR 和 Western blot 分析 GLO1 水平，用 Methylglyoxal Assay Kit 测量 MG 水平。通过旷场和嗅探持续时间测试评估 VPA 小鼠的兴趣和焦虑。通过三箱、埋珠和尾巴刺痛测试来确定 VPA 小鼠的社交能力、重复行为和痛觉阈值。我们的结果表明，VPA 小鼠中 GLO1 增加，MG 减少。GLO1 抑制剂--溴苄基谷胱甘肽环戊基二酯（BrBzGCp2）的给药有利于缓解焦虑、减少重复行为，并改善 VPA 小鼠受损的社交能力和痛觉阈值。BrBzGCp2 治疗可能成为 ASD 患者有前景的治疗策略。
