Institute for Cognitive Science Studies (ICSS), Tehran, Iran.
Institute for Cognitive Science Studies (ICSS), Tehran, Iran; Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.
Neurotoxicol Teratol. 2018 May-Jun;67:1-9. doi: 10.1016/j.ntt.2018.02.002. Epub 2018 Feb 24.
Aim Thimerosal, a mercury-containing preservative has been widely used in a number of biological and drug products, including many vaccines, and has been studied as a possible etiological factor for some neurodevelopmental disabilities. Here, the protective effects of Alpha Lipoic Acid (ALA), an organosulfur compound derived from Octanoic Acid, on Thimerosal-induced behavioral abnormalities in rat were examined.
108 male Wistar rats were divided into three cohorts and treated as follows: 1) Thimerosal at different doses (30, 300, or 3000 μg Hg/kg) in four i.m. injections on 7, 9, 11, 15postnatal days. 2) ALA (at doses of 5, 10 and 20 mg/kg), following the same order; 3) single dose of Thimerosal (3000 μg Hg/kg) plus ALA at different doses (5, 10 or 20 mg/kg), by the previously described method. A saline treated control group and a ALA vehicle control (0.1% NaOH) were also included. At 5 and 8 weeks after birth, rats were evaluated with behavioral tests, to assess locomotor activity, social interactions and stereotyped behaviors, respectively.
The data showed that Thimerosal at all doses (30, 300 and 3000 μg Hg/kg) significantly impacted locomotor activity. Thimerosal at doses of 300 and 3000 but not 30 μg Hg/kg impaired social and stereotyped behaviors. In contrast, ALA (at doses of 5, 10 and 20 mg/kg) did not alter behaviors by itself, at doses of 20 mg/kg, it reduced social interaction deficits induced by the highest dose of Thimerosal (3000 μg Hg/kg). Moreover, ALA, at all doses prevented the adverse effects of Thimerosal on stereotyped behaviors.
the results of this preclinical study, consistent with previous studies on mice and rats, reveals that neonatal dose-dependent exposure to Thimerosal mimicking the childhood vaccine schedule can induce abnormal social interactions and stereotyped behaviors similar to those observed in neurodevelopmental disorders such as autism, and, for the first time, revealed that these abnormalities may be ameliorated by ALA. This indicates that ALA may protect against mercurial-induced abnormal behaviors.
硫柳汞，一种含汞的防腐剂，已被广泛应用于多种生物制品和药物中，包括许多疫苗，并被研究为某些神经发育障碍的可能病因。在这里，我们研究了来自辛酸的有机硫化合物α-硫辛酸（ALA）对硫柳汞诱导的大鼠行为异常的保护作用。
108 只雄性 Wistar 大鼠分为三组，如下处理：1）不同剂量的硫柳汞（30、300 或 3000μgHg/kg），在 7、9、11、15 日龄时通过 4 次肌肉注射。2）ALA（剂量为 5、10 和 20mg/kg），按相同顺序；3）单次 3000μgHg/kg 硫柳汞加不同剂量（5、10 或 20mg/kg）ALA，采用上述方法。还包括盐水处理对照组和 ALA 载体对照组（0.1%NaOH）。出生后 5 和 8 周，通过行为测试评估大鼠，分别评估运动活动、社会互动和刻板行为。
数据显示，所有剂量（30、300 和 3000μgHg/kg）的硫柳汞均显著影响运动活动。300 和 3000μgHg/kg 的硫柳汞但不是 30μgHg/kg 的剂量会损害社会和刻板行为。相比之下，ALA（5、10 和 20mg/kg）本身不会改变行为，20mg/kg 的剂量可减少 3000μgHg/kg 最高剂量硫柳汞引起的社会互动缺陷。此外，ALA 可预防所有剂量的硫柳汞对刻板行为的不良影响。
这项临床前研究的结果与以前在小鼠和大鼠上的研究一致，表明模仿儿童疫苗方案的新生儿剂量依赖性暴露于硫柳汞可以诱导类似于自闭症等神经发育障碍的异常社会互动和刻板行为，并且首次表明这些异常可能通过 ALA 得到改善。这表明 ALA 可能预防汞引起的异常行为。
