Exposure to methylmercury results in serum autoantibodies to neurotypic and gliotypic proteins.
Environmental exposure to methylmercury (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 (lg) 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 lg to all 5 proteins, not normally seen in controls. For anti-NFs and anti-GFAP, lgM isotype predominated significantly (p < 0.05) over lgG. lg for MBP were of the lgG isotype, lgM were not detected. Significant differences (p < 0.05) between 16 and 32 ppm MeHg in levels of anti-NF 68 and GFAP, lgM, were evident at 7 days of exposure, but not at 14 days. Anti-NF 160, lgM, 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 lgG 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.
el-Fawal
H A
HA
Nelson Institute of Environmental Medicine, New York University Medical Center, Tuxedo Park 10987 USA.
Gong
Z
Z
Little
A R
AR
Evans
H L
HL
D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008767:Methylmercury Compounds / Q000633:toxicity*; D004676:Myelin Basic Protein / Q000276:immunology*; D009419:Nerve Tissue Proteins / Q000276:immunology*; D016900:Neurofilament Proteins / Q000276:immunology*; D051381:Rats; D011916:Rats, Inbred F344
D001323:Autoantibodies; D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008767:Methylmercury Compounds; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; C066858:neurofilament protein NF 68