Corticosterone enhances chlorpyrifos-induced neuroinflammation

Details

• Personal Author:
  Kelly KA ; Lasley SM ; Miller DB ; O'Callaghan JP
• Description:
  Elevated expression of proinflammatory mediators in the CNS serves as the basis for normal and pathophysiological neuroinflammation. For example, the enhanced expression of proinflammatory cytokines and chemokines such as TNF-alpha, IL-1beta, IL-6 and CCL2 may underlie the general malaise termed sickness behavior as well as depression and can affect and contribute to a risk of neurodegeneration in affected individuals. Chemical exposures that increase the degree or duration of proinflammatory responses in the CNS may lead to more severe symptoms and consequences of neuroinflammation. Our prior data indicate that acute exposure of the C57Bl6/J mouse to the irreversible cholinesterase inhibitor, diisopropylfluorophosphate (DFP), results in a neuroinflammatory response in multiple brain regions, as evidenced by enhanced expression of a large variety of proinflammatory cytokines over a 12-hr post exposure period. Surprisingly, treatment with anti-inflammatory glucocorticoid, corticosterone (CORT), enhanced rather than suppressed DFP-induced neuroinflammation. These findings suggested that CORT might serve as a stressor surrogate to "prime" the neuroinflammatory response to workplace and environmentally relevant exposures to organophosphates, such as the widely used pesticide, chlorpyrifos (CPF). Here, we administered CPF (8 mg/kg, i.p.) with and without prior CORT (400 microg/ml in the drinking water for 4 days) to C57Bl6/J male mice. As with DFP, CPF alone caused neuroinflammation (increases in mRNA for TNF-alpha, LIF, CCL2 and OSM) at 6 hrs. post dosing. These effects were markedly enhanced by the prior exposure to CORT and broadened to include another cytokine (IL-1beta) . These findings suggest that stressors experienced by pesticide applicators and other workers exposed to CPF will contribute to a neuroinflammatory response of yet to be characterized duration or severity. [Description provided by NIOSH]
• Subjects:
  Adrenal Cortex Hormones Animals Environmental Monitoring Immune System Insecticides Laboratories Nervous System Occupational Health Organophosphates Safety
• Keywords:
  Animal-studies Author Keywords: Glia Brain-function Cellular-reactions Central-nervous-system Corticoids Corticosteroids Exposure-assessment Immune-reaction Laboratory-animals Laboratory-testing Neuroinflammation Neurological-reactions Neurotoxic-effects Neurotoxicity Organo-phosphorus-pesticides Pesticides

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• Publisher:
  Society for Neuroscience
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  District of Columbia ; 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
• NIOSHTIC Number:
  nn:20045491
• Citation:
  Neuroscience 2014: 44th Annual Meeting of the Society for Neuroscience, November 15 - 19, 2014, Washington, DC. Washington, DC: Society for Neuroscience, 2014 Nov; :423.14/Z7
• CAS Registry Number:
  Chlorpyrifos (CAS RN 2921-88-2) ; Diisopropyl fluorophosphate (CAS RN 55-91-4)
• Federal Fiscal Year:
  2015
• Peer Reviewed:
  False
• Source Full Name:
  Neuroscience 2014: 44th Annual Meeting of the Society for Neuroscience, November 15 - 19, 2014, Washington, DC
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:38d576d6aa27f264e214fc24d6b955b10166712f4b9e9f1c98ff8050ce45745764c7d2a6844096bf29f950c5530d8cdb66438e755937eaea58b82e9fbe91041a
• Download URL:
  https://stacks.cdc.gov/view/cdc/200893/cdc_200893_DS1.pdf
• File Type:
  [PDF - 113.11 KB ]