Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-4-4
pubmed:abstractText
Chronic stress and extended periods of elevated circulating glucocorticoids have been reported to exacerbate excitotoxicity-induced hippocampal neuronal injury in rat. Despite continued interest in the effects of protracted exposure to stress or glucocorticoids, there has been little examination of how other types of neurotoxicity may be exacerbated or blocked, by stress. Here we examined the effects of chronic supraphysiologic levels of corticosterone on D-3,4-methylenedioxymethamphetamine (D-MDMA)-induced striatal dopaminergic neurotoxicity in the female C57BL/6J mouse. Corticosterone (5 mg, 15 mg or placebo) pellets were implanted to continuously elevate circulating glucocorticoids and create a model of the ultimate effect of chronic activation of the hypothalamic-pituitary-adrenal axis. After 7 days, a neurotoxic regimen of D-MDMA was administered (20 mg/kg s.c. every 2 hx4); thymus, spleen, striatum and hippocampus were collected 72 h later. Significant involution of thymus and spleen confirmed the bioavailability of the corticosterone at both dosages. D-MDMA increased the striatal levels of the astrocyte-localized protein glial fibrillary acidic protein (GFAP, a marker of gliosis); both dosages of corticosterone exacerbated this increase but only the 15 mg pellet exacerbated the decrease in tyrosine hydroxylase protein. Corticosterone alone or in combination with D-MDMA produced no neural injury in hippocampus, as measured by GFAP. Our work indicates corticosterone was able to increase the vulnerability of the striatum, but not the hippocampus to D-MDMA. An examination of other mouse strains and models of neurotoxic injury would be useful in determining the general validity of the glucocorticoid neuroendangerment hypothesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-8993
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
933
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
130-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11931857-Adrenergic Uptake Inhibitors, pubmed-meshheading:11931857-Animals, pubmed-meshheading:11931857-Body Temperature, pubmed-meshheading:11931857-Corticosterone, pubmed-meshheading:11931857-Dopamine, pubmed-meshheading:11931857-Dose-Response Relationship, Drug, pubmed-meshheading:11931857-Down-Regulation, pubmed-meshheading:11931857-Drug Administration Schedule, pubmed-meshheading:11931857-Drug Interactions, pubmed-meshheading:11931857-Female, pubmed-meshheading:11931857-Glial Fibrillary Acidic Protein, pubmed-meshheading:11931857-Hippocampus, pubmed-meshheading:11931857-Hydroxyindoleacetic Acid, pubmed-meshheading:11931857-Hypothalamo-Hypophyseal System, pubmed-meshheading:11931857-Immune System, pubmed-meshheading:11931857-Mice, pubmed-meshheading:11931857-Mice, Inbred C57BL, pubmed-meshheading:11931857-N-Methyl-3,4-methylenedioxyamphetamine, pubmed-meshheading:11931857-Neostriatum, pubmed-meshheading:11931857-Neurons, pubmed-meshheading:11931857-Neurotoxins, pubmed-meshheading:11931857-Organ Size, pubmed-meshheading:11931857-Serotonin, pubmed-meshheading:11931857-Stress, Physiological, pubmed-meshheading:11931857-Tyrosine 3-Monooxygenase
pubmed:year
2002
pubmed:articleTitle
Chronic treatment with supraphysiological levels of corticosterone enhances D-MDMA-induced dopaminergic neurotoxicity in the C57BL/6J female mouse.
pubmed:affiliation
Chronic Stress and Molecular Neurotoxicology Laboratories, Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health/Centers for Disease Control, 1095 Willowdale Road, Morgantown, WV 26505, USA. edj2@cdc.gov
pubmed:publicationType
Journal Article