Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, San Luis Potosí, Mexico.
División de Neurociencias, Centro de Investigación Biomédica de Occidente, IMSS. Guadalajara, Jalisco, Mexico.
Neurotox Res. 2021 Dec;39(6):1970-1980. doi: 10.1007/s12640-021-00409-y. Epub 2021 Sep 17.
There is solid epidemiological evidence that arsenic exposure leads to cognitive impairment, while experimental work supports the hypothesis that it also contributes to neurodegeneration. Energy deficit, oxidative stress, demyelination, and defective neurotransmission are demonstrated arsenic effects, but it remains unclear whether synaptic structure is also affected. Employing both a triple-transgenic Alzheimer's disease model and Wistar rats, the cortical microstructure and synapses were analyzed under chronic arsenic exposure. Male animals were studied at 2 and 4 months of age, after exposure to 3 ppm sodium arsenite in drinking water during gestation, lactation, and postnatal development. Through nuclear magnetic resonance, diffusion-weighted images were acquired and anisotropy (integrity; FA) and apparent diffusion coefficient (dispersion degree; ADC) metrics were derived. Postsynaptic density protein and synaptophysin were analyzed by means of immunoblot and immunohistochemistry, while dendritic spine density and morphology of cortical pyramidal neurons were quantified after Golgi staining. A structural reorganization of the cortex was evidenced through high-ADC and low-FA values in the exposed group. Similar changes in synaptic protein levels in the 2 models suggest a decreased synaptic connectivity at 4 months of age. An abnormal dendritic arborization was observed at 4 months of age, after increased spine density at 2 months. These findings demonstrate alterations of cortical synaptic connectivity and microstructure associated to arsenic exposure appearing in young rodents and adults, and these subtle and non-adaptive plastic changes in dendritic spines and in synaptic markers may further progress to the degeneration observed at older ages.
有确凿的流行病学证据表明，砷暴露会导致认知障碍，而实验工作支持这样一种假设，即砷也会导致神经退行性变。能量不足、氧化应激、脱髓鞘和神经传递缺陷是砷的已知作用，但尚不清楚突触结构是否也受到影响。本研究采用三重转基因阿尔茨海默病模型和 Wistar 大鼠，在慢性砷暴露下分析皮质的微观结构和突触。雄性动物在妊娠、哺乳期和产后发育期间饮用含 3ppm 亚砷酸钠的饮用水，在 2 个月和 4 个月大时进行研究。通过磁共振，获取扩散加权图像，并得出各向异性（完整性；FA）和表观扩散系数（弥散程度；ADC）指标。通过免疫印迹和免疫组织化学分析突触后密度蛋白和突触小体蛋白，通过高尔基染色后对皮质锥体细胞的树突棘密度和形态进行量化。暴露组的高 ADC 和低 FA 值表明皮质结构发生了重组。两种模型中突触蛋白水平的相似变化表明，4 个月大时突触连接减少。在 2 个月大时增加树突棘密度后，在 4 个月大时观察到异常的树突分支。这些发现表明，在年轻的啮齿动物和成年动物中，砷暴露会导致皮质突触连接和微观结构发生改变，而树突棘和突触标志物的这些微妙的非适应性可塑性变化可能会进一步发展为老年时观察到的退行性变。
