Methylmercury (MeHg) is a potent neurotoxic chemical, and gestational exposure to MeHg is known to cause developmental impairments in fetuses. Although it is well established that fetuses are extremely susceptible to MeHg toxicity, limited studies have investigated the effect of low-level MeHg exposure on mothers. In this study, we demonstrated that exposure of pregnant rats to low-level MeHg (1 ppm in drinking water) induced cerebellar synaptic and neuritic remodeling during the perinatal period between gestational day 20 and postnatal day (PND) 1. MeHg-induced neurodegeneration, for example, cerebellar granule cell death, was not detected and fetuses were delivered normally and exhibited normal development. The maternal cerebellar synaptic and neuritic changes were restored by PND 21. To elucidate the mechanisms underlying these perinatal changes in MeHg-exposed pregnant rats, we investigated proteins related to synapse formation and neurite outgrowth. We identified suppression of the tropomyosin receptor kinase (Trk) A pathway and reduced activity-regulated cytoskeleton-associated protein (Arc) expression in MeHg-exposed pregnant rats during the perinatal period, mirroring the decreased expression of synaptic and neuritic proteins. MeHg-exposed pregnant rats also exhibited increased perinatal plasma corticosterone levels and decreased estradiol levels compared to vehicle-exposed pregnant rats. Similar to the synaptic and neuritic changes, TrkA pathway activity, Arc expression, and plasma hormone levels were subsequently normalized. These results suggest that exposure of pregnant rats to low-level MeHg affected perinatal cerebellar synaptic and neuritic remodeling through modulation of the TrkA pathway and Arc expression which may be caused by MeHg-induced hormonal changes.

中文翻译：

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暴露于低水平甲基汞的怀孕大鼠在围产期表现出小脑突触和神经炎重塑。

甲基汞 (MeHg) 是一种强效神经毒性化学物质，已知妊娠期接触甲基汞会导致胎儿发育障碍。尽管众所周知，胎儿极易受到甲基汞毒性的影响，但有限的研究调查了低水平甲基汞暴露对母亲的影响。在这项研究中，我们证明了在妊娠第 20 天和产后第 (PND) 1 之间的围产期，怀孕大鼠暴露于低水平的甲基汞（饮用水中 1 ppm）会诱导小脑突触和神经炎重塑。甲基汞诱导的神经变性，例如，未检测到小脑颗粒细胞死亡，胎儿正常分娩并表现出正常发育。PND 21 恢复了母体小脑突触和神经炎的变化。为了阐明暴露于甲基汞的怀孕大鼠围产期变化的潜在机制，我们研究了与突触形成和神经突生长相关的蛋白质。我们确定了围产期暴露于甲基汞的怀孕大鼠中原肌球蛋白受体激酶 (Trk) A 通路的抑制和活性调节的细胞骨架相关蛋白 (Arc) 表达的降低，这反映了突触和神经炎蛋白的表达降低。与暴露于载体的妊娠大鼠相比，暴露于甲基汞的妊娠大鼠还表现出围产期血浆皮质酮水平升高和雌二醇水平降低。与突触和神经炎变化类似，TrkA 通路活性、Arc 表达和血浆激素水平随后被标准化。