Description:
<jats:sec><jats:label /><jats:p>Nitrosative stress induced by NO overproduction in neurons and glia contributes to neuronal death. However, NO underproduction impaires blood supply to brain cells and aggravates neurodegeneration. In this study, we tested whether NO is detrimental or protective in experimental AD (EAD) modeled in rats by bilateral injection of a toxic β‐amyloid (Aβ) fragment (25–35) into magnocellular nucleus. Memory was evaluated using a conditioned passive avoidance test. NO production was assessed by the plasma level of nitrite and nitrate. During development of EAD rats were injected with a NO synthase inhibitor L‐NNA or a NO donor, dinitrosyl iron complex, DNIC. NO production was significantly decreased in rats with EAD. L‐NNA potentiated the detrimental effect of Aβ and induced memory retention disorders. In contrast, DNIC prevented memory impairment. Resistance to Aβ toxicity was compared in Wistar and August rats, which have lower and higher rates of NO synthesis, respectively. Memory disorders were virtually absent in August rats, and the number of dead neurons in brain cortex was significantly less in August than in Wistar rats. Therefore, reduced NO production in the body plays an important role in development of cognitive disorders induced by Aβ treatment while higher levels of NO may be protective in EAD. Support: Russian Foundation for Basic Research, grant 07‐04‐00650.</jats:p></jats:sec>