Nitric oxide synthase alteration induced by chronic stress exposition in mouse hippocampus. Participation in stress induced deficit in memory.

MARÌA LAURA PALUMBO; MARÍA A ZORRILLA ZUBILETE; LAURA RUTH GUELMAN; GRACIELA ALICIA CREMASCHI; ANA MARÍA GENARO

Buenos Aires

Congreso; XXII CONGRESO LATINOAMERICANO Y 1RO IBEROAMERICANO DE CIENCIAS FISIOLÓGICAS.; 2006

Sociedad Argentina de Fisiología

Exposure to adverse situations affects an important number of aspects of our daily life. While response to stress is a necessary survival mechanism, prolonged stress can have several repercussion, such as impairments in learning and memory. Nitric oxide (NO) has been involved in many pathophysiological brain processes including hippocampal responses to stress. However, the exact role of NO in the cognitive deficit associated to chronic stress exposition has not been elucidated. Here we investigated the participation of hippocampal NO production by constitutive and inducible isoforms of NOS in the memory impairment induced in mice subjected to a chronic mild stress model (CMS). CMS mice showed a poor learning performance in both open field and passive avoidance inhibitory task respect to control mice. On the other hand chronic stress induced a diminished NO production. This decrease was due to calcium dependent nNOS activity as eNOS increased in CMS animals. Besides, NO production by iNOS isoform was not detected. These results were according to western-blot evaluation of protein levels. The magnitude of oxidative stress, measured by reactive oxygen species (ROS) production, after excitotoxic levels of NMDA, was increased in hippocampus of CMS mice. Moreover, basal and stimulated ROS formation were higher in the presence of both, general NOS inhibitor and selective nNOS inhibitor, in control and CMS mice. The addition of co-factors for optimal NOS activity decreased both, basal and stimulated, levels of ROS. Finally, administration of L-NAME to non-exposed animals induced similar behavioral and neurochemical alterations that those observed in CMS mice. These results suggest a novel role for nNOS showing protective activity against insults that trigger tissue toxicity leading to memory impairments.