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Protracted exposure to supraphysiological levels of corticosterone does not cause neuronal loss or damage and protects against kainic acid-induced neurotoxicity in the hippocampus of C57BL/6J mice.

Authors
Benkovic-A; O'Callaghan-JP; Miller-DB
Source
Neurotoxicology 2009 Nov; 30(6):965-976
NIOSHTIC No.
20036270
Abstract
High levels of stress or stress hormones have been reported to exacerbate a variety of human disorders of the cardiovascular, gastrointestinal, immune, reproductive, and nervous systems. In rats, high glucocorticoid levels have been reported to cause neuronal death and injury as well as enhance susceptibility to neurotoxic agents and attenuate repair mechanisms: however, the impact of high dosages of CORT in mice has not been fully evaluated. We investigated the ability of supraphysiological levels of CORT to cause hippocampal neuronal death, and to modulate the neurotoxicity of kainic acid (KA) in male C57BL/6J mice. Timed-release CORT pellets (10, 35, 100 mg/21 d) were implanted subcutaneously in the back of mice, and the sustained release of glucocorticoid caused involution of the thymus and decreased the weight of the spleen. Kainic acid caused stage 1 seizures that were unaffected by CORT; however, steroid treatment decreased KA-associated mortality. Little neuronal damage was detected by the cupric-silver neurodegeneration stain. Neurotoxicity caused by an intraperitoneal injection of 25 mg/kg KA was attenuated by seven days of CORT pre-treatment. The KA-induced increase in cupric-silver staining, reactive gliosis, microglial activation, and blood-brain barrier disruption was attenuated indicating neuroprotection. Our data indicate supraphysiological levels of CORT do not cause neuronal death or injury in hippocampus of C57BL/6J mice and provide neuroprotection against KA-induced neural damage.
Keywords
Exposure assessment; Exposure-methods; Gastrointestinal-system; Gastrointestinal-system-disorders; Heart; Hormone-activity; Immune-system; Immune-system-disorders; Laboratory-animals; Laboratory-testing; Nervous-system-disorders; Nervous-system-function; Neurophysiological-effects; Neurotoxic-effects; Physiological-effects; Stress; Author Keywords: Blood-brain barrier; Excitotoxicity; Glia; Neurodegeneration; Neuroprotection; Stress
Contact
Diane B. Miller, HELD/TMBB CDC/NIOSH, Mail Stop 3014, 1095 Willowdale Road, Morgantown, WV 26505
CODEN
NRTXDN
Publication Date
20091101
Document Type
Journal Article
Email Address
zcg9@cdc.gov
Funding Type
Cooperative Agreement
Fiscal Year
2010
NTIS Accession No.
NTIS Price
Identifying No.
Cooperative-Agreement-Number-U60-OH-008466
Issue of Publication
6
ISSN
0161-813X
NIOSH Division
HELD
Source Name
Neurotoxicology
State
WV; MI
Performing Organization
Michigan State University
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