BACKGROUND AND AIM: Thimerosal (THIM) is a mercury-containing preservative widely used in many biological and medical products including many vaccines. It has been accused of being a possible etiological factor for some neurodevelopmental disorders such as autistic spectrum disorders (ASDs). In our study, the potential therapeutic effect of montelukast, a leukotriene receptor antagonist used to treat seasonal allergies and asthma, on THIM mice model (ASDs model) was examined. METHODOLOGY Newborn mice were randomly distributed into three groups: (Group 1) Control (Cont.) group received saline injections. (Group 2) THIM-treated (THIM) group received THIM intramuscular (IM) at a dose of 3000 μg Hg/kg on postnatal days 7, 9, 11, and 15. (Group 3) Montelukast-treated (Monte) group received THIM followed by montelukast sodium (10 mg/kg/day) intraperitoneal (IP) for 3 weeks. Mice were evaluated for growth development, social interactions, anxiety, locomotor activity, and cognitive function. Brain histopathology, alpha 7 nicotinic acetylcholine receptors (α7nAChRs), nuclear factor kappa B p65 (NF-κB p65), apoptotic factor (Bax), and brain injury markers were evaluated as well. RESULTS THIIM significantly impaired social activity and growth development. Montelukast mitigated THIM-induced social deficit probably through α7nAChRs upregulation, NF-κB p65, Bax, and brain injury markers downregulation, thus suppressing THIM-induced neuronal toxicity and inflammation. CONCLUSION Neonatal exposure to THIM can induce growth retardation and abnormal social interactions similar to those observed in ASDs. Some of these abnormalities could be ameliorated by montelukast via upregulation of α7nAChRs that inhibited NF-κB activation and significant suppression of neuronal injury and the associated apoptosis.

中文翻译：

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孟鲁司特在减轻小鼠出生后早期施用硫柳汞引起的自闭症行为方面的新型潜在治疗效用。

背景和目的：硫柳汞 (THIM) 是一种含汞防腐剂，广泛用于许多生物和医疗产品，包括许多疫苗。它被指责为某些神经发育障碍（如自闭症谱系障碍 (ASD)）的可能病因。在我们的研究中，检测了孟鲁司特（一种用于治疗季节性过敏和哮喘的白三烯受体拮抗剂）对 THIM 小鼠模型（ASD 模型）的潜在治疗效果。方法学新生小鼠随机分为三组：（组1）对照（继续）组接受盐水注射。（第 2 组）THIM 治疗（THIM）组在出生后第 7、9、11 和 15 天以 3000 μg Hg/kg 的剂量接受 THIM 肌肉注射（IM）。(第 3 组) 孟鲁司特治疗 (Monte) 组接受 THIM 和孟鲁司特钠 (10 毫克/千克/天) 腹膜内 (IP) 3 周。评估小鼠的生长发育、社交互动、焦虑、运动活动和认知功能。还评估了脑组织病理学、α 7 烟碱型乙酰胆碱受体 (α7nAChRs)、核因子κB p65 (NF-κB p65)、凋亡因子 (Bax) 和脑损伤标志物。结果 THIIM 显着损害了社会活动和生长发育。孟鲁司特可能通过 α7nAChRs 上调、NF-κB p65、Bax 和脑损伤标志物下调来减轻 THIM 诱导的社会缺陷，从而抑制 THIM 诱导的神经元毒性和炎症。结论 新生儿暴露于 THIM 可导致生长迟缓和异常社交互动，类似于在 ASD 中观察到的那些。孟鲁司特可以通过上调抑制 NF-κB 活化和显着抑制神经元损伤和相关细胞凋亡的 α7nAChRs 来改善其中一些异常。