Corticosterone primes the neuroinflammatory response to DFP in mice: potential animal model of Gulf War Illness

Details

• Personal Author:
  Kelly KA ; Lasley SM ; Locker AR ; Miller DB ; O'Callaghan JP
• Description:
  Gulf War Illness (GWI) is a multi-symptom disorder with features characteristic of persistent sickness behavior. Among conditions encountered in the GW theater were physiological stressors (e.g., heat/cold/physical activity/sleep deprivation), prophylactic treatment with the reversible AChE inhibitor, pyridostigmine bromide (PB), the insect repellent, DEET, and potentially the nerve agent, sarin. Prior exposure to the anti-inflammatory glucocorticoid, CORT, at levels associated with high physiological stress, can paradoxically prime the CNS to produce a robust proinflammatory response to neurotoxicants and systemic inflammation; such neuroinflammatory effects can be associated with sickness behavior. Here, we examined whether CORT primed the CNS to mount neuroinflammatory responses to GW exposures as a potential model of GWI. Male C57BL/6 mice were treated with chronic (14d) PB/DEET, subchronic (7-14d) CORT, and acute exposure (day 15) to diisopropyl fluorophosphate (DFP), a sarin surrogate and irreversible AChE inhibitor. DFP alone caused marked brain-wide neuroinflammation assessed by qPCR of TNF-alpha, IL6, CCL2, IL-1beta, LIF and OSM. Pretreatment with high physiological levels of CORT greatly augmented (up to 300-fold) the neuroinflammatory responses to DFP. Anti-inflammatory pretreatment with minocycline suppressed many proinflammatory responses to CORT+DFP. Our findings are suggestive of a possible critical, yet unrecognized interaction between the stressor/environment of the GW theater and agent exposure(s) unique to this war. Such exposures may in fact prime the CNS to amplify future neuroinflammatory responses to pathogens, injury or toxicity. Such occurrences could potentially result in the prolonged episodes of sickness behavior observed in GWI. [Description provided by NIOSH]
• Subjects:
  Animals Behavior Laboratories Nervous System Occupational Health Safety Sleep Sleep Initiation And Maintenance Disorders
• Keywords:
  Author Keywords: CORT DFP GWI Insect-repellents Laboratory-animals Microglia Military Personnel Minocycline Nerve-function Nerves Neuroinflammation Physical-exercise Physical-fitness Physical-stress Physiological-stress Physiology Sleep-deprivation Stress

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• ISSN:
  0022-3042
• Document Type:
  Text
• Genre:
  Journal Article
• 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:
  133
• Issue:
  5
• NIOSHTIC Number:
  nn:20046012
• Citation:
  J Neurochem 2015 Jun; 133(5):708-721
• Contact Point Address:
  James P. O'Callaghan, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Mailstop L-3014, Morgantown, WV 26505, USA
• Email:
  jdo5@cdc.gov
• CAS Registry Number:
  Diisopropyl fluorophosphate (CAS RN 55-91-4)
• Federal Fiscal Year:
  2015
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Neurochemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:eb15668d4c19af4ac592b22401c511b61b7258f1903576aef7ab55a981061bbffa43bdb7b97ddce4be537563dfc9fd26411a3470192395a04736f642e0d00395
• Download URL:
  https://stacks.cdc.gov/view/cdc/201205/cdc_201205_DS1.pdf
• File Type:
  [PDF - 1.57 MB ]