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1400 W ameliorates acute hypobaric hypoxia/reoxygenation-induced cognitive deficits by suppressing the induction of inducible nitric oxide synthase in rat cerebral cortex microglia
- Source :
- Behavioural Brain Research. 319:188-199
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Nitric oxide (NO) is involved in neuronal modifications, and overproduction of NO contributes to memory deficits after acute hypobaric hypoxia-reoxygenation. This study investigated the ability of the iNOS inhibitor 1400W to counteract spatial memory deficits following acute hypobaric hypoxia-reoxygenation, and to affect expression of NOS, NO, 3-NT and MDA production, and apoptosis in rat cerebral cortex. We also used primary rat microglia to investigate the effect of 1400W on expression of NOS, NO, 3-NT and MDA production, and apoptosis. Acute hypobaric hypoxia-reoxygenation impaired spatial memory, and was accompanied by activated microglia, increased iNOS expression, NO, 3-NT and MDA production, and neuronal cell apoptosis in rat cerebral cortex one day post-reoxygenation. 1400W treatment inhibited iNOS expression without affecting nNOS or eNOS. 1400W also reduced NO, 3-NT and MDA production, and prevented neuronal cell apoptosis in cerebral cortex, in addition to reversing spatial memory impairment after acute hypobaric hypoxia-reoxygenation. Hypoxia-reoxygenation activated primary microglia, and increased iNOS and nNOS expression, NO, 3-NT, and MDA production, and apoptosis. Treatment with 1400W inhibited iNOS expression without affecting nNOS, reduced NO, 3-NT and MDA production, and prevented apoptosis in primary microglia. Based on the above findings, we concluded that the highly selective iNOS inhibitor 1400W inhibited iNOS induction in microglial cells, and reduced generation of NO, thereby mitigating oxidative stress and neuronal cell apoptosis in the rat cerebral cortex, and improving the spatial memory dysfunction caused by acute hypobaric hypoxia-reoxygenation.
- Subjects :
- 0301 basic medicine
Nitric Oxide Synthase Type II
Apoptosis
Nerve Tissue Proteins
Pharmacology
Nitric Oxide
medicine.disease_cause
Nitric oxide
Rats, Sprague-Dawley
03 medical and health sciences
Behavioral Neuroscience
chemistry.chemical_compound
0302 clinical medicine
Enos
Malondialdehyde
medicine
Animals
Annexin A5
Hypoxia
Maze Learning
Cells, Cultured
biology
Microglia
Hypoxia (medical)
biology.organism_classification
Rats
Oxygen
Nitric oxide synthase
Disease Models, Animal
030104 developmental biology
medicine.anatomical_structure
Gene Expression Regulation
chemistry
Cerebral cortex
Immunology
biology.protein
Tyrosine
Imines
Lipid Peroxidation
medicine.symptom
Cognition Disorders
030217 neurology & neurosurgery
Oxidative stress
Subjects
Details
- ISSN :
- 01664328
- Volume :
- 319
- Database :
- OpenAIRE
- Journal :
- Behavioural Brain Research
- Accession number :
- edsair.doi.dedup.....dc72e07460863bfc905bc1a5bb27585d