el-Fawal H A, Gong Z, Little A R, Evans H L
Nelson Institute of Environmental Medicine, New York University Medical Center, Tuxedo Park 10987, USA.
Neurotoxicology. 1996 Spring;17(1):267-76.
Environmental exposure to methyl mercury (MeHg) continues to pose a threat to humans, making early detection of neurotoxic effects a pressing concern. An enzyme-linked immunosorbent assay (ELISA) to measure serum autoantibodies (Ig) to neurotypic and gliotypic proteins [neurofilament triplet (NF68; NF160; NF200), myelin basic protein (MBP) and glial fibrillary acid protein (GFAP)] as markers of subclinical neurotoxicity was developed and tested in Fisher 344 rats exposed orally to 16 or 32 ppm MeHg. Both levels of MeHg resulted in serum Ig to all 5 proteins, not normally seen in controls. For anti-NFs and anti-GFAP, IgM isotype predominated significantly (p < 0.05) over IgG.Ig for MBP were of the IgG isotype, IgM were not detected. Significant differences (p < 0.05) between 16 and 32 ppm MeHg in levels of anti-NF 68 and GFAP, IgM, were evident at 7 days of exposure, but not at 14 days. Anti-NF 160, IgM, was significantly (p < 0.01) elevated in rats exposed to 32 ppm vs 16 ppm at 14 days. However, at both dose levels anti-NF 68 titers were the most elevated of the three NF proteins (p < 0.0001). For anti-NF 200 and anti-MBP it was the IgG isotype that was significantly (p < 0.01) elevated in the 32 ppm group at 7 days. GFAP levels as a marker of neurotoxicity were determined in the cortex, hippocampus and cerebellum. Exposure to 32ppm MeHg resulted in decreased (p < 0.05) levels in the cortex at 14 days. Both levels of MeHg resulted in increased GFAP in the cerebellum at 14 days. This study suggests that assay of autoantibodies against nervous system proteins may provide a means of assessing the early neurotoxic effects of environmental MeHg exposure.
环境中甲基汞(MeHg)的暴露持续对人类构成威胁,因此早期检测神经毒性效应成为一个紧迫问题。我们开发了一种酶联免疫吸附测定(ELISA)方法,用于测量血清中针对神经型和胶质型蛋白[神经丝三联体(NF68、NF160、NF200)、髓鞘碱性蛋白(MBP)和胶质纤维酸性蛋白(GFAP)]的自身抗体(Ig),以此作为亚临床神经毒性的标志物,并在经口暴露于16或32 ppm甲基汞的Fisher 344大鼠中进行了测试。两种甲基汞水平均导致血清中出现针对所有5种蛋白的Ig,而在对照组中通常未见此种情况。对于抗神经丝蛋白(anti-NFs)和抗GFAP,IgM亚型显著占主导(p < 0.05),超过IgG。针对MBP的Ig为IgG亚型,未检测到IgM。在暴露7天时,16 ppm和32 ppm甲基汞组之间抗NF 68和GFAP的IgM水平存在显著差异(p < 0.05),但在14天时无差异。在14天时,暴露于32 ppm甲基汞的大鼠中抗NF 160的IgM显著升高(p < 0.01),而暴露于16 ppm甲基汞的大鼠中该指标未升高。然而,在两个剂量水平下,抗NF 68的滴度在三种神经丝蛋白中升高最为明显(p < 0.0001)。对于抗NF 200和抗MBP,在7天时,32 ppm组的IgG亚型显著升高(p < 0.01)。作为神经毒性标志物的GFAP水平在皮质、海马体和小脑中进行了测定。暴露于32 ppm甲基汞导致14天时皮质中GFAP水平降低(p < 0.05)。两种甲基汞水平均导致14天时小脑中GFAP升高。这项研究表明,检测针对神经系统蛋白的自身抗体可能为评估环境中甲基汞暴露的早期神经毒性效应提供一种方法。