Prior Exposure to Stress Hormone Exacerbates the Neuroinflammatory Response to the Nerve Agent Sarin and Pesticide Dichlorvos in a Mouse Model of Gulf War Illness

Details

• Personal Author:
  Kelly KA ; Lasley SM ; Michalovicz LT ; Miller DB ; O'Callaghan JP
• Description:
  Ongoing research into the underlying cause of Gulf War Illness (GWI) has repeatedly indicated a role for persistent aberrant neuroinflammatory signaling associated with neurotoxicant exposure; veterans with GWI had the potential for exposure to several neurotoxicants in theater. Our prior research using a GWI animal model has indicated that exposure to organophosphate acetylcholinesterase inhibitors (OP AChEIs), such as the sarin surrogate diisopropyl fluorophosphate (DFP) or the pesticide chlorpyrifos, following administration of exogenous corticosterone (CORT) to mimic high physiological stress experienced in theater, results in robust neuroinflammation. In our effort to expand upon these results, we investigated if: 1) our DFP results were representative of nerve agent exposure; 2) CORT priming affected another OP AChEI pesticide, dichlorvos (DDVP). In this study, mice were given CORT (200 mg/L) in the drinking water for 7 days followed by exposure to sarin (LD20=100 micro g/kg, s.c.) or DDVP (20 mg/kg, i.p.). Cytokine expression was evaluated in the brain by qPCR (sarin and DDVP) and serum by multiplex ELISA (sarin) at 6 hours post-exposure. Like DFP and chlorpyrifos, exposure to sarin or DDVP following CORT resulted in a significant increase in brain cytokine mRNA. However, CORT + sarin only significantly increased three (IL-6, IL-12, and IL-17) of the 16 serum cytokines, compared to all other conditions. These data indicate that every known OP AChEI that veterans with GWI may have encountered in theater carries the potential to produce exacerbated neuroinflammation. The parallels between our observations with DFP and sarin validates the use of DFP as a surrogate to nerve agent in animal models. While these experiments focus on an acute exposure paradigm, the neuroinflammatory profile observed here has been demonstrated to align with the aberrant neuroimmune state associated with GWI and has been shown to facilitate detrimental responses to future inflammatory challenges. This suggests that exposure to any OP AChEIs under conditions of high physiological stress was likely to cause or contribute to the development of GWI and warrants continued investigation regarding their long-term effects as it pertains to GWI. [Description provided by NIOSH]
• Subjects:
  Animals Environmental Exposure Insecticides Laboratories Nervous System Occupational Health Risk Assessment Risk Factors Safety Toxicology
• Keywords:
  Exposure Levels Laboratory Animals Military Personnel Models Nerve Damage Neurological Diseases Neurological System Neurotoxic Agents Pesticides Physiological Effects Physiological Stress Risk Factors Sarin

  More +
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Illinois ; OSHA Region 3 ; OSHA Region 5 ; 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:20062271
• Citation:
  Toxicologist 2021 Mar; 180(S1):312
• CAS Registry Number:
  Dichlorvos (CAS RN 62-73-7) ; Diisopropyl fluorophosphate (CAS RN 55-91-4) ; Sarin (CAS RN 107-44-8)
• Federal Fiscal Year:
  2021
• 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-512:272e4055305c2efb3eeebd1731214ba410a9fb637087357f6f476ae8d5e909885f2b1bb1b0e7e0f5f136460ffa1b4df3b2ced7c3cd4f6e839ce80eb4db4da380
• Download URL:
  https://stacks.cdc.gov/view/cdc/225552/cdc_225552_DS1.pdf
• File Type:
  [PDF - 141.17 KB ]