INVESTIGADORES
CREMASCHI Graciela Alicia
congresos y reuniones científicas
Título:
Nitric oxide synthase alteration induced by chronic stress exposition in mouse hippocampus. Participation in stress induced deficit in memory
Autor/es:
MARÍA L PALUMBO; MARÍA ZORRILLA-ZUBILETTE; L. GUELMAN; GRACIELA A CREMASCHI; ANA M GENARO
Lugar:
Buenos Aires, Argentina
Reunión:
Congreso; XXII Latin-American and 1st Ibero-American Congress of Physiological Sciences; 2006
Institución organizadora:
Sociedad Argentina de Fisiología
Resumen:
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.