Changes in hippocampal gene expression by 7-nitroindazole in rats submitted to forced swimming stress

Autor(es)

Ferreira, F. R. ^[1] ; Oliveira, A. M. ^[2] ; Dinarte, A. R. ^{[3, 4, 5, 6]} ; Pinheiro, D. G. ^{[3, 4, 5, 6]} ; Greene, L. J. ^[2] ; Silva, Jr., W. A. ^{[3, 4, 5, 6]} ; Joca, S. R. ^[7] ; Guimaraes, F. S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Pharm, Sch Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ctr Prot Chem, Hemoctr Ribeirao Preto, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Natl Inst Sci & Technol Stem Cell & Cell Therapy, Ribeirao Preto, SP - Brazil

^[4] Ctr Cell Therapy, Ribeirao Preto, SP - Brazil

^[5] Reg Blood Ctr, Ribeirao Preto, SP - Brazil

^[6] Univ Sao Paulo, Dept Genet, Sch Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP - Brazil

^[7] Univ Sao Paulo, Dept Chem & Phys, Pharmacol Lab, Sch Pharmaceut Sci Ribeirao Preto, BR-14049900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: GENES BRAIN AND BEHAVIOR; v. 11, n. 3, p. 303-313, APR 2012.
• Citações Web of Science: 11

Resumo

Nitric oxide (NO) is an atypical neurotransmitter that has been related to the pathophysiology of major depression disorder. Increased plasma NO levels have been reported in depressed and suicidal patients. Inhibition of neuronial nitric oxide synthase (nNOS), on the other hand, induces antidepressant effects in clinical and pre-clinical trials. The mechanisms responsible for the antidepressant-like effects of nNOS inhibitors, however, are not completely understood. In this study, genomic and proteomic analyses were used to investigate the effects of the preferential nNOS inhibitor 7-nitroindazole (7-NI) on changes in global gene and protein expression in the hippocampus of rats submitted to forced swimming test (FST). Chronic treatment (14 days, i.p.) with imipramine (15 mg/kg daily) or 7-NI (60 mg/kg daily) significantly reduced immobility in the FST. Saturation curves for Serial analysis of gene expression libraries showed that the hippocampus of animals submitted to FST presented a lower number of expressed genes compared to non-FST stressed groups. Imipramine, but not 7-NI, reverted this effect. GeneGo analyses revealed that genes related to oxidative phosphorylation, apoptosis and survival controlled by HTR1A signaling and cytoskeleton remodeling controlled by Rho GTPases were significantly changed by FST. 7-NI prevented this effect. In addition, 7-NI treatment changed the expression of genes related to transcription in the cAMP response element-binding pathway. Therefore, this study suggests that changes in oxidative stress and neuroplastic processes could be involved in the antidepressant-like effects induced by nNOS inhibition. (AU)

• Processo FAPESP: 05/55925-2 - Análise do padrão de expressão gênica global do hipocampo de ratos submetidos a tratamento com inibidor da sintase neuronial do óxido nítrico por tecnologia SAGE
• Beneficiário: Frederico Rogério Ferreira
• Linha de fomento: Bolsas no Brasil - Doutorado