Corticosterone Regulates Expression of CCL2 in the Intact and Chemically Injured Hippocampus

Details

• Personal Author:
  Little AR ; O'Callaghan JP ; Sriram K
• Description:
  Expression of the chemokine (C-C motif) ligand 2 (CCL2), also known as, monocyte chemoattractant protein (MCP)-1, increases in response to disease-, trauma-, or toxicant-induced damage to the central nervous system (CNS). In the periphery, endogenous and exogenous glucocorticoids are known to suppress CCL2 expression associated with inflammatory conditions. However, such actions of glucocorticoids on CCL2 expression in the CNS remain unknown. Here, we explored the effects of the glucocorticoid, corticosterone (CORT), on the expression of CCL2 and its receptors, CCR2 and CCR5, in the hippocampal formation using intact, adrenalectomized (ADX) and trimethyltin (TMT)-treated rats. An immunosuppressive regimen of CORT did not alter the mRNA expression of CCL2 or its receptors in the hippocampus. ADX, however, markedly increased the expression of CCL2 and CCR2 mRNAs in the hippocampus, while CORT replacement reversed the effects of ADX on CCL2 gene expression. Hippocampal damage resulting from systemic administration of the organometallic neurotoxicant, TMT, was associated with microglial activation, as evidenced by enhanced expression of microglial markers integrin alphaM (CD11b) and F4/80, as well as, microglia-associated factors, CCL2 and IL-1alpha. An immunosuppressive dose of CORT, suppressed TMT-induced expression of CCL2. Given the association of CCL2 with microglial activation, it appears that CORT may play a role in regulating microglial activation. However, CORT treatment did not alter TMT-mediated neuronal damage and astrogliosis. Such observations suggest that injury-related expression of microglia-associated chemokines and cytokines may subserve a role unrelated to neuronal damage. In summary, our data indicate that in the CNS, CCL2 gene expression is under negative regulation by glucocorticoids. [Description provided by NIOSH]
• Subjects:
  Nervous System Nervous System Diseases Nervous System Disorders Occupational Health Safety
• Keywords:
  Central-nervous-system-disorders Nervous-system-disorders Neurotoxic-effects Neurotoxicity Neurotoxins Proteins
• ISSN:
  0304-3940
• 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
• Pages in Document:
  162-166
• Volume:
  399
• Issue:
  1
• NIOSHTIC Number:
  nn:20030268
• Citation:
  Neurosci Lett 2006 May; 399(1-2):162-166
• Contact Point Address:
  Molecular Neurotoxicology Laboratory, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, CDC-NIOSH, TMBB-HELD, MS 3014, 1095 Willowdale Road, Morgantown, WV 26505, USA
• Email:
  jdo5@cdc.gov
• Federal Fiscal Year:
  2006
• Peer Reviewed:
  True
• Source Full Name:
  Neuroscience Letters
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d7265d5b8a53b1f93a63a28557066932d8167c7d2a248da656c96db810f4b8a55176db8803d7f7353d53ef0f7caf8e5a634cab69b893c8eb285dfc8d0f3c5d76
• Download URL:
  https://stacks.cdc.gov/view/cdc/190988/cdc_190988_DS1.pdf
• File Type:
  [PDF - 160.75 KB ]