CSF Proteome as Circulating Biomarkers of Neurotoxicity
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Neurotoxicity has been linked to exposure to a number of drugs and chemicals, yet efficient, predictive, and minimally-invasive methods to detect it are lacking. Fluid-based biomarkers such as those found in serum, plasma, urine, and cerebrospinal fluid (CSF) have great potential due to the relative ease of sampling, but at present, data on their expression and translation are lacking or inconsistent. Here, we present data on biomolecules that have promise for detection and characterization of neurotoxicity induced by the known neurotoxic agent, trimethyltin (TMT). A single dose of TMT (7 mg/kg, ip) to the rat led to significant alterations in markers of neuroinflammation detectable in CSF, and a proteomic analysis reflected significant alterations in signaling molecules related to neurotoxicity. A total of 352 proteins were identified. TMT samples contained between 29-237 proteins that were significantly different from controls. Network analysis determined that TMT treatment resulted in higher levels of proteins associated with neurological disease and cellular assembly and lower levels of proteins associated with cell survival as compared to controls. These findings provide an opportunity to explore the correlation of these fluid biomarkers with traditional neuropathology and magnetic resonance imaging (MRI) that serve to define TMT-induced neurotoxicity. Our data demonstrate a comprehensive correlation of TMT-induced neuropathology with potential neurotoxicity biomarkers and MRI-based endpoints, findings suggestive of an involvement of specific pathways that can be assessed using peripheral fluids.