Previous studies in both humans and animals have demonstrated the presence of serum autoantibodies to neurotypic (e.g., neurofilament triplet [NF]) and gliotypic proteins (myelin basic protein (MBP) and glial fibrillary acidic protein [GFAP]) following exposure to some heavy metals or organophosphorus compounds.These studies suggest a correlation with exposure and clinical deficits. The neurotoxic organometal, TMT, has been used as a denervation tool to validate the enhanced expression of GFAP as a biomarker astrogliosis resulting from neuronal damage and cell death. In the present study TMT was used to assess detection of serum autoantibodies as peripheral marker of neurotoxicity. Male Long-Evans rats (45 days of age) were administered either TMT (8 mg/kg; sc; n=16) or an equal volume of sterile 0.9% saline (n=16). Five weeks post administration, serum was collected and rats were sacrificed for collection of brains. Serum autoantibodies (both IgM and IgG isotypes) to NF68, NF160, NF200, MBP and GFAP were assayed using an ELISA. Saline rats did not have detectable levels of autoantibodies.Only sera from TMT-exposed rats had detectable titers of autoantibodies to NFs with IgG, the isotype associated with secondary challenge and pathology, predominating. Anti-NF68 titers were highest (600 + 75 ng/ml) compared to NF160 (85 + 15 ng/ml) or NF200 (160 + 45 ng/ml). Autoantibodies to MBP and GFAP were also detected, however, they were predominantly IgM, the isotype associated with primary challenge or recent injury. Hippocampal GFAP, detected at this time, was significantly (p<0.05) higher (300%) than in control brains indicating astrogliosis. The detection of anti-NF, as indicative of neuronal insult, was consistent with loss of hippocampal neurons in CA3c and CA4. This study suggests that detection of autoantibodies to neurotypic and gliotypic proteins may be used to indicate chemical neurotoxicity. (Supported by NIH HD35965).
The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California