CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
artículos
Título:
Loss of hippocampal neuronal nitric oxide synthase contributes to the stress related-deficit in learning and memory
Autor/es:
MARÍA LAURA PALUMBO; NICOLAS FOSSER; HUGO RÍOS; MARÍA A ZORRILLA ZUBILETE; LAURA RUTH GUELMAN; GRACIELA ALICIA CREMASCHI; ANA MARÍA GENARO
Revista:
JOURNAL OF NEUROCHEMISTRY
Editorial:
Blackwell Publishing
Referencias:
Año: 2007 vol. 102 p. 261 - 274
ISSN:
0022-3042
Resumen:
Nitric oxide (NO) has been involved in many pathophysiological brain processes. However, the exact role of NO in the cognitive deficit associated to chronic stress exposure has not been elucidated. In this study, we investigated the participation of hippocampal NO production and their regulation by protein kinase C (PKC) in the memory impairment induced in mice subjected to chronic mild stress model (CMS). CMSmice showed a poor learning performance in both open field and passive avoidance inhibitory task respect to control mice. Histological studies showed a morphological alteration in the hippocampus of CMS mice. On the other hand, chronic stress induced a diminished NO production by neuronal nitric oxide synthase (nNOS) correlated with an increment in gamma and zeta PKC isoenzymes. Partial restoration of nNOS activity was obtained after PKC activity blockade. NO production by inducible nictric oxide synthase isoform was not detected. Themagnitude of oxidative stress, evaluated by reactive oxygen species production, after excitotoxic levels of NMDA was increased in hippocampus of CMS mice. Moreover, ROS formation was higher in the presence of nNOS inhibitor in both control and CMS mice. Finally, treatment of mice with nNOS inhibitors results in behavioural alterations similar to those observed in CMS animals. These findings suggest a novel role for nNOS showing protective activity against insults that trigger tissue toxicity leading to memory impairments.