Prior Exposure to Corticosterone Markedly Enhances and Prolongs the Neuroinflammatory Response to Systemic Challenge with LPS

Details

• Personal Author:
  Castranova, Vincent ; Kelly KA ; Michalovicz LT ; Miller DB ; Miller JV ; O'Callaghan JP
• Description:
  Systemic exposure to the inflammagen and bacterial endotoxin lipopolysaccharide (LPS) has been widely used to evaluate inflammation and sickness behavior. While many inflammatory conditions occur in the periphery, it is well established that peripheral inflammation can affect the brain. Neuroinflammation, the elaboration of proinflammatory mediators in the CNS, commonly is associated with behavioral symptoms (e.g., lethargy, anhedonia, anorexia, depression, etc.) termed sickness behavior. Stressors have been shown to interact with and alter neuroinflammatory responses and associated behaviors. Here, we examined the effects of the stress hormone, corticosterone (CORT), as a stressor mimic, on neuroinflammation induced with a single injection (2mg/kg, s.c.) or inhalation exposure (7.5 microg/m3) of LPS or polyinosinic:polycytidylic acid (PIC; 12mg/kg, i.p.) in adult male C57BL/6J mice. CORT was given in the drinking water (200 mg/L) for 1 week or every other week for 90 days followed by LPS. Proinflammatory cytokine expression (TNFalpha, IL-6, CCL2, IL-1beta, LIF, and OSM) was measured by qPCR. The activation of the neuroinflammation downstream signaling activator, STAT3, was assessed by immunoblot of pSTAT3Tyr705. The presence of astrogliosis was assessed by immunoassay of GFAP. Acute exposure to LPS caused brain-wide neuroinflammation without producing astrogliosis; exposure to CORT for 1 week caused marked exacerbation of the LPS-induced neuroinflammation. This neuroinflammatory "priming" by CORT was so pronounced that sub-neuroinflammatory exposures by inhalation instigated neuroinflammation when paired with prior CORT exposure. This effect also was extended to another common inflammagen, PIC (a viral mimic). Furthermore, a single week of CORT exposure maintained the potential for priming for 30 days, while intermittent exposure to CORT for up to 90 days synergistically primed the LPS-induced neuroinflammatory response. These findings highlight the possibility for an isolated inflammatory event to be exacerbated by a temporally distant stressful stimulus and demonstrates the potential for recurrent stress to greatly aggravate chronic inflammatory disorders. [Description provided by NIOSH]
• Subjects:
  Endocrine System Immune System Laboratories Lipids Occupational Health Safety
• Keywords:
  Central Nervous System Corticosteroids Cytokines Hormone Activity Hormones Immune Reaction Immune System Laboratory Animals Lipopolysaccharide Neurological System Stress

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• ISSN:
  1932-6203
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; 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:
  13
• Issue:
  1
• NIOSHTIC Number:
  nn:20050835
• Citation:
  PLoS One 2018 Jan; 13(1):e0190546
• Contact Point Address:
  James P. O'Callaghan, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Morgantown, West Virginia
• Email:
  Jdo5@cdc.gov
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  PLoS One
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:69803ccad11f1cec7d13a5e83628dcb0d74a35f394d75dfc6a93f5d23efdcdc5b843cebf12c5c3268b2674eac850cab887cde83aa03c0f05437c174aa14f2fd9
• Download URL:
  https://stacks.cdc.gov/view/cdc/211036/cdc_211036_DS1.pdf
• File Type:
  [PDF - 2.25 MB ]