LOSS OF HIPPOCAMPAL NEURONAL NITRIC OXIDE SYNTHASE CONTRIBUTES TO THE STRESS RELATED DEFICIT IN LEARNING AND MEMORY

MARÍA L PALUMBO; NICOLÁS S FOSSER; HUGO RIOS; MARÍA A ZORRILLA ZUBILETE; LAURA R GUELMAN; GRACIELA A CREMASCHI; ANA M GENARO

JOURNAL OF NEUROCHEMISTRY

Blackwell Synergy

Año: 2007 vol. 102 p. 261 - 274

0022-3042

AbstractNitric oxide (NO) has been involved in many pathophysiologicalbrain processes. However, the exact role of NO in thecognitive deficit associated to chronic stress exposure has notbeen elucidated. In this study, we investigated the participationof hippocampal NO production and their regulation byprotein kinase C (PKC) in the memory impairment induced inmice subjected to chronic mild stress model (CMS). CMSmice showed a poor learning performance in both open fieldand passive avoidance inhibitory task respect to control mice.Histological studies showed a morphological alteration in thehippocampus of CMS mice. On the other hand, chronic stressinduced a diminished NO production by neuronal nitric oxidesynthase (nNOS) correlated with an increment in gamma andzeta PKC isoenzymes. Partial restoration of nNOS activitywas obtained after PKC activity blockade. NO production byinducible nictric oxide synthase isoform was not detected. Themagnitude of oxidative stress, evaluated by reactive oxygenspecies production, after excitotoxic levels of NMDA wasincreased in hippocampus of CMS mice. Moreover, ROSformation was higher in the presence of nNOS inhibitor in bothcontrol and CMS mice. Finally, treatment of mice with nNOSinhibitors results in behavioural alterations similar to thoseobserved in CMS animals. These findings suggest a novel rolefor nNOS showing protective activity against insults that triggertissue toxicity leading to memory impairments.