CSF Proteome as Fluidic Biomarkers of Neurotoxicity

Details

• Personal Author:
  Aschner M ; Burks SM ; Hanig JP ; He Z ; Herr DW ; Imam SZ ; Liachenko S ; O'Callaghan JP ; Pardo ID ; Paule MG ; Pierson J ; Raymick J ; Roberts R ; Rogstad S ; Slikker W Jr. ; Somps C
• Description:
  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 with TMT treatment. 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. [Description provided by NIOSH]
• Subjects:
  Biomarkers Body Fluids Nervous System Occupational Health Safety Toxicology
• Keywords:
  Body Fluids Cerebrospinal Fluid Magnetic Resonance Imaging MRI Neurological Diseases Neurological System Neurotoxic Agents Proteins Sampling Methods
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Arkansas ; Connecticut ; District of Columbia ; Maryland ; New York ; North Carolina ; OSHA Region 1 ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 6 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  180
• NIOSHTIC Number:
  nn:20062269
• Citation:
  Toxicologist 2021 Mar; 180(S1):187
• CAS Registry Number:
  Trimethylstannane (CAS RN 1631-73-8)
• Federal Fiscal Year:
  2021
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 60th Annual Meeting and ToxExpo, March 12-26, 2021, Virtual Event
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:77be31517604ca79c82192325d8bf5758623d5ca936f584a4cc52edccbefc97ae594e79b8b90358ac401f97baee8f9e5ef19203c3b2e16e86a7a289dc1bac190
• Download URL:
  https://stacks.cdc.gov/view/cdc/225550/cdc_225550_DS1.pdf
• File Type:
  [PDF - 146.41 KB ]