Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, People's Republic of China.
Toxicology. 2013 Jan 7;303:43-53. doi: 10.1016/j.tox.2012.10.024. Epub 2012 Nov 9.
The main purpose of this study was to test the hypothesis that arsenite induces neurotoxicity via effects on astrocytes. Astrocytes were exposed to 0, 5 or 10 μM arsenite in medium for 24 h, and then astrocyte-conditioned medium (ACM) was collected after incubation with fresh medium for 6 h. Primary neuron cultures were divided into four groups due to ACM, which were neurons without ACM exposure (group I) and neurons exposed to ACM from 0, 5 or 10 μM arsenite treated astrocytes (group II-IV). Protein expression of N-methyl-d-aspartate receptors (NR1, NR2A, NR2B), calmodulin-dependent protein kinase II (CaMKII) and adenylate cyclase (AC) in neurons were measured after incubation with ACM for 4, 8 or 12 h. Morphological changes and synaptic formation were observed after a 72 h-incubation with ACM. Compared to group II, synaptic formation and protein expression of NR2A, NR2B, CaMKII and AC in group III and IV were significantly suppressed. Moreover, synaptic formation and protein expression of CaMKII and AC in group II were significantly enhanced when compared with group I. Taken together, findings from this study suggested that arsenic in astrocytes might impair synaptic formation through disturbing astrocytic effects on neuronal signal transduction.
本研究的主要目的是验证亚砷酸盐通过对星形胶质细胞的影响诱导神经毒性的假说。将星形胶质细胞暴露于 0、5 或 10μM 亚砷酸盐的培养基中 24 小时，然后在孵育新鲜培养基 6 小时后收集星形胶质细胞条件培养基（ACM）。由于 ACM，将原代神经元培养物分为四组，分别为未暴露于 ACM 的神经元（第 I 组）和暴露于来自 0、5 或 10μM 亚砷酸盐处理的星形胶质细胞的 ACM 的神经元（第 II-IV 组）。在孵育 ACM 4、8 或 12 小时后，测量神经元中 N-甲基-D-天冬氨酸受体（NR1、NR2A、NR2B）、钙调蛋白依赖性蛋白激酶 II（CaMKII）和腺苷酸环化酶（AC）的蛋白表达。在孵育 ACM 72 小时后观察形态变化和突触形成。与第 II 组相比，第 III 组和第 IV 组的突触形成和 NR2A、NR2B、CaMKII 和 AC 的蛋白表达明显受到抑制。此外，与第 I 组相比，第 II 组的突触形成和 CaMKII 和 AC 的蛋白表达明显增强。总之，这项研究的结果表明，星形胶质细胞中的砷可能通过干扰星形胶质细胞对神经元信号转导的影响来损害突触形成。
