Laboratório de Farmacologia Molecular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém 66075-110, Brazil.
Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK.
Int J Mol Sci. 2021 Oct 7;22(19):10855. doi: 10.3390/ijms221910855.
Human exposure to methylmercury (MeHg) is currently high in regions such as the Amazon. Understanding the molecular changes associated with MeHg-induced neurotoxicity and the crosstalk with the periphery is essential to support early diagnoses. This work aimed to evaluate cellular and molecular changes associated with behavioral alterations in MeHg acute exposure and the possible changes in extracellular vesicles (EVs) number and S100β content. Adults male Wistar rats were orally treated with 5 mg/kg for four days. Behavioral performance, molecular and histological changes in the cerebellum, and plasma EVs were assessed. MeHg-intoxicated animals performed significantly worse in behavioral tests. MeHg increased the number of GFAP+ cells and GFAP and S100β mRNA expression in the cerebellum but no change in NeuN+ or IBA-1+ cells number was detected. The number of exosomes isolated from plasma were decreased by the metal. S100B mRNA was detected in circulating plasma EVs cargo in MeHg exposure. Though preliminary, our results suggest astrocytic reactivity is displaying a protective role once there was no neuronal death. Interestingly, the reduction in exosomes number could be a new mechanism associated with MeHg-induced neurotoxicity and plasma EVs could represent a source of future biomarkers in MeHg intoxication.
人类暴露于甲基汞(MeHg)的情况目前在亚马逊地区等地区很高。了解与 MeHg 诱导的神经毒性相关的分子变化以及与外围的串扰对于支持早期诊断至关重要。这项工作旨在评估与 MeHg 急性暴露相关的行为改变以及细胞外囊泡(EVs)数量和 S100β 含量可能发生的变化相关的细胞和分子变化。成年雄性 Wistar 大鼠连续 4 天经口给予 5mg/kg MeHg。评估行为表现、小脑的分子和组织学变化以及血浆 EVs。MeHg 中毒动物在行为测试中表现明显更差。MeHg 增加了小脑内 GFAP+细胞和 GFAP 和 S100β mRNA 的表达,但未检测到 NeuN+或 IBA-1+细胞数量的变化。从血浆中分离的外泌体数量减少。MeHg 暴露时,S100B mRNA 存在于循环血浆 EVs 载物中。虽然初步,但我们的结果表明,星形胶质细胞反应显示出一种保护作用,因为没有神经元死亡。有趣的是,外泌体数量的减少可能是与 MeHg 诱导的神经毒性相关的新机制,而血浆 EVs 可能代表 MeHg 中毒中未来生物标志物的来源。