Inorganic arsenic is among the major contaminants of groundwater in the world. Worldwide population-based studies demonstrate that chronic arsenic exposure is associated with poor cognitive performance among children and adults, while research in animal models confirms learning and memory deficits after arsenic exposure. The aim of this study was to investigate the long-term effects of environmentally relevant arsenic exposure in the myelination process of the prefrontal cortex (PFC) and corpus callosum (CC). A longitudinal study with repeated follow-up assessments was performed in male Wistar rats exposed to 3 ppm sodium arsenite in drinking water. Animals received the treatment from gestation until 2, 4, 6, or 12 months of postnatal age. The levels of myelin basic protein (MBP) were evaluated by immunohistochemistry/histology and immunoblotting from the PFC and CC. As plausible alterations associated with demyelination, we considered mitochondrial mass (VDAC) and two axonal damage markers: amyloid precursor protein (APP) level and phosphorylated neurofilaments. To analyze the microstructure of the CC in vivo, we acquired diffusion-weighted images at the same ages, from which we derived metrics using the tensor model. Significantly decreased levels of MBP were found in both regions together with significant increases of mitochondrial mass and slight axonal damage at 12 months in the PFC. Ultrastructural imaging demonstrated arsenic-associated decreases of white matter volume, water diffusion anisotropy, and increases in radial diffusivity. This study indicates that arsenic exposure is associated with a significant and persistent negative impact on microstructural features of white matter tracts.

无机砷是世界上地下水的主要污染物之一。全球范围内基于人口的研究表明，慢性砷暴露与儿童和成人的不良认知表现有关，而动物模型研究证实，砷暴露后学习和记忆缺陷。这项研究的目的是调查环境相关的砷暴露对额叶前皮层（PFC）和体（CC）髓鞘化过程的长期影响。在暴露于饮用水中3 ppm亚砷酸钠的雄性Wistar大鼠中进行了一项具有反复随访评估的纵向研究。动物从妊娠直到出生后的2、4、6或12个月接受治疗。通过免疫组织化学/组织学和从PFC和CC进行的免疫印迹评估了髓磷脂碱性蛋白（MBP）的水平。作为与脱髓鞘相关的合理变化，我们考虑了线粒体质量（VDAC）和两个轴突损伤标记：淀粉样蛋白前体蛋白（APP）水平和磷酸化的神经丝。分析CC的微观结构在体内，我们获取了相同年龄的扩散加权图像，然后使用张量模型从中得出指标。在两个区域中，在PFC中发现MBP的水平显着下降，同时线粒体质量显着增加，并且轴突受到轻微损伤。超微结构成像显示砷相关的白质体积减少，水扩散各向异性和径向扩散率增加。这项研究表明，砷暴露与对白质束微结构特征的重大而持久的负面影响有关。