Supraphysiological Levels of Coticosterone and Kainic Acid: Failure to Find Increased Hippocampal Neurotoxicity in the Kainate Resistant C57BL/6J Mouse

Details

• Personal Author:
  Benkovic SA ; Callaghan JPO ; Miller DB
• Description:
  Chronic stress mediated through glucocorticoids has been shown to exacerbate neurotoxicity in susceptible populations. To evaluate the role of glucocorticoids in the effects of chronic stress on neurotoxicity, as well as the role of strain in toxicant susceptibility, supraphysiological dosages of corticosterone (CORT)(200 mg/90d release pellet, s.c. implant) and its interactions with kainic acid (KA) neurotoxicity were examined in non-susceptible C57BI/6J mice. Dose-response comparisons between the KA susceptible strain FVB/N and C57BI/6J mice revealed a 25mg/kg (i.p.) dosage caused differential patterns of seizures in the two strains with FVB mice averaging 4 (Racine scale of 1 - 6) while C57 mice averaged 1. KA produced substantial CAI cell loss in FVB/N mice accompanied by elevations in the injury related marker of astrocytic hypertrophy, GFAP (673% over control, seven day survival), while C57BI/6J mice displayed no observable cell loss and only minor elevations in GFAP (44% over control, seven day survival). CORT exposure for four weeks prior to KA caused marked decreases in thymic and spleen, but not body weights. No overt cell loss was observed in CORT exposed mice, but GFAP was down-regulated in hippocampus as assessed by ELISA and diminished immunohisrochemical signal. CORT pretreatment did not alter the GFAP response observed after KA treatment, or produce identifiable hippocampal cell loss. Our data confirm that CORT down-regulates GFAP in mouse brain and that there are differences in the susceptibility of mouse strains to KA-induced hippocampal damage. These results suggest that stress will not increase the neurotoxic effects of KA, other excitotoxicants, or potentially, other hippocampal insults in the resistant C57B1/6J mouse. It is likely that individuals genetically susceptible to a given toxicant may be more prone to stress-induced exacerbation of toxicity. [Description provided by NIOSH]
• Subjects:
  Laboratories Nervous System Nervous System Diseases Occupational Health Safety
• Keywords:
  Laboratory-animals Neurological-diseases Neurological-reactions Neurological-system Neurotoxicity Stress
• ISSN:
  1096-6080
• Publisher:
  Oxford University Press
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; 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:
  60
• Issue:
  1
• NIOSHTIC Number:
  nn:20021968
• Citation:
  Toxicologist 2001 Mar; 60(1):372
• Federal Fiscal Year:
  2001
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 40th Annual Meeting, March 25-29, 2001, San Francisco, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5be7aa90d524581b546298046236672c62fe8396827831c00faa0b3ac56408098612c54542cc5da26de467687ecca0ef52c4cfd965768f940b7e1b9f8e9d1008
• Download URL:
  https://stacks.cdc.gov/view/cdc/199020/cdc_199020_DS1.pdf
• File Type:
  [PDF - 186.95 KB ]