Alteration of expression levels of neuronal nitric oxide synthase and haemoxygenase-2 messenger RNA in the hippocampi and cortices of young adult and aged cognitively unimpaired and impaired Long-Evans rats

Neuronal nitric oxide synthase and haem oxygenase-2 are postulated to be im portant enzymes involved in neuronal transmission and modulation of free ra dical levels in neurons. Hippocampal and cortical neuronal nitric oxide syn thase and haem oxygenase-2 expressions were compared in young adult (6 mont hs) and aged (24-26 months) Long-Evans rats. Aged rats were assigned as eit her cognitively unimpaired or impaired based on their performances in the M orris water maze behavioural task. In situ hybridization revealed increased neuronal nitric oxide synthase messenger RNA levels in selected regions of the hippocampi and cortices of aged rats. Moreover, aged cognitively impai red animals showed significantly higher neuronal nitric oxide synthase mess enger RNA expression than aged cognitively unimpaired animals in several br ain regions. For haem oxygenase-2 mRNA expressions, both young and aged cog nitively impaired rats showed increased expressions in hippocampi compared with aged cognitively unimpaired rats, while no difference was found in cor tices between all three animal groups. The increase in neuronal nitric oxid e synthase messenger RNA expression levels in the aged animals may be relat ed to increased free radical production occurring in ageing. Alternatively, elevated neuronal nitric oxide synthase and haem oxygenase-2 messenger RNA expressions may represent compensatory responses to oxidative stress and a ge-related changes in neuronal functions. Regarding cognitive status, aged cognitively impaired rats showed significant spatial memory deficits relati ve to young and aged cognitively unimpaired rats. Our data suggest a correlation between age-related cognitive impairment and change in messenger RNA expressions for the neuronal nitric oxide synthase and haem oxygenase-2 systems in brain areas implicated in learning and mem ory processes. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.