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Chronic Stress Induces the Expression of Inducible Nitric Oxide Synthase in Rat Brain Cortex
Author(s) -
Olivenza Raquel,
Moro María A.,
Lizasoain Ignacio,
Lorenzo Pedro,
Fernández Ana P.,
Rodrigo José,
Boscá Lisardo,
Leza Juan C.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.740785.x
Subject(s) - nitric oxide synthase , nitrotyrosine , peroxynitrite , neuroprotection , nitric oxide , glutamate receptor , neurodegeneration , lactate dehydrogenase , chemistry , cerebral cortex , oxidative stress , medicine , endocrinology , western blot , chronic stress , cortex (anatomy) , biology , biochemistry , pharmacology , neuroscience , enzyme , superoxide , receptor , disease , gene
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 NO 2 ‐ + NO 3 ‐ (NO x ‐ ) 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 NO x ‐ 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.