NITRIC OXIDE SYNTHASE ALTERATION INDUCED BY CHRONIC STRESS EXPOSITION IN MOUSE HIPPOCAMPUS. PARTICIPATION IN STRESS INDUCED DEFICIT IN MEMORY

MARÍA L PALUMBO; MARÍA ZORRILLA-ZUBILETTE; LAURA GUELMAN; GRACIELA A CREMASCHI; ANA M GENARO

Buenos Aires, Argentina

Congreso; XXII Congreso Latinoamericano y I Iberoamericano de Ciencias Fisiológicas.; 2006

Sociedad Argentina de Fisiología

POS 10-16Nitric oxide synthase alteration induced bychronic stress exposition in mouse hippocampus.Participation in stress induced deficit inmemory. María L Palumbo, María Zorrilla-Zubilette, Laura Guelman, Graciela A Cremaschi,Ana M Genaro. Centro de Estudios Farmacológicosy Botánicos (CEFYBO)-CONICET-Universidadde Buenos Aires, Argentina.Exposure to adverse situations affects an importantnumber of aspects of our daily life. While response tostress is a necessary survival mechanism, prolongedstress can have several repercussion, such as impairmentsin learning and memory. Nitric oxide (NO) hasbeen involved in many pathophysiological brain processesincluding hippocampal responses to stress. However,the exact role of NO in the cognitive deficit associatedto chronic stress exposition has not been elucidated.Here we investigated the participation of hippocampalNO production by constitutive and inducibleisoforms of NOS in the memory impairment induced inmice subjected to a chronic mild stress model (CMS).CMS mice showed a poor learning performance in bothopen field and passive avoidance inhibitory task respectto control mice. On the other hand chronic stress induceda diminished NO production. This decrease wasdue to calcium dependent nNOS activity as eNOS increasedin CMS animals. Besides, NO production byiNOS isoform was not detected. These results wereaccording to western-blot evaluation of protein levels.The magnitude of oxidative stress, measured by reactiveoxygen species (ROS) production, after excitotoxiclevels of NMDA, was increased in hippocampus ofCMS mice. Moreover, basal and stimulated ROS formationwere higher in the presence of both, general NOSinhibitor and selective nNOS inhibitor, in control andCMS mice. The addition of co-factors for optimal NOSactivity decreased both, basal and stimulated, levels ofROS. Finally, administration of L-NAME to nonexposedanimals induced similar behavioral and neurochemicalalterations that those observed in CMS mice.These results suggest a novel role for nNOS showingprotective activity against insults that trigger tissuetoxicity leading to memory impairments.