Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-2-10
pubmed:abstractText
Long-term exposure to stress has detrimental effects on several brain functions in many species, including humans, and leads to neurodegenerative changes. However, the underlying neural mechanisms by which stress causes neurodegeneration are still unknown. We have investigated the role of endogenously released nitric oxide (NO) in this phenomenon and the possible induction of the inducible NO synthase (iNOS) isoform. In adult male rats, stress (immobilization for 6 h during 21 days) increases the activity of a calcium-independent NO synthase and induces the expression of iNOS in cortical neurons as seen by immunohistochemical and western blot analysis. Three weeks of repeated immobilization increases immunoreactivity for nitrotyrosine, a nitration product of peroxynitrite. Repeated stress causes accumulation of the NO metabolites NO2+ NO3- (NOx-) accumulation in cortex, and these changes occur in parallel with lactate dehydrogenase (LDH) release and impairment of glutamate uptake in synaptosomes. Administration of the selective iNOS inhibitor aminoguanidine (400 mg/kg i.p. daily from days 7 to 21 of stress) prevents NOx- accumulation in cortex, LDH release, and impairment of glutamate uptake in synaptosomes. Taken together, these findings indicate that a sustained overproduction of NO via iNOS expression may be responsible, at least in part, for some of the neurodegenerative changes caused by stress and support a possible neuroprotective role for specific iNOS inhibitors in this situation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
74
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
785-91
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10646531-Animals, pubmed-meshheading:10646531-Blotting, Western, pubmed-meshheading:10646531-Calcium, pubmed-meshheading:10646531-Cerebral Cortex, pubmed-meshheading:10646531-Chronic Disease, pubmed-meshheading:10646531-Glutamic Acid, pubmed-meshheading:10646531-Immunohistochemistry, pubmed-meshheading:10646531-L-Lactate Dehydrogenase, pubmed-meshheading:10646531-Male, pubmed-meshheading:10646531-Nitrates, pubmed-meshheading:10646531-Nitric Oxide Synthase, pubmed-meshheading:10646531-Nitric Oxide Synthase Type II, pubmed-meshheading:10646531-Nitrites, pubmed-meshheading:10646531-Rats, pubmed-meshheading:10646531-Rats, Wistar, pubmed-meshheading:10646531-Restraint, Physical, pubmed-meshheading:10646531-Stress, Physiological, pubmed-meshheading:10646531-Synaptosomes, pubmed-meshheading:10646531-Tyrosine
pubmed:year
2000
pubmed:articleTitle
Chronic stress induces the expression of inducible nitric oxide synthase in rat brain cortex.
pubmed:affiliation
Departamento de Farmacología, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't