Law A, Doré S, Blackshaw S, Gauthier S, Quirion R
Department of Neurology and Neurosurgery, McGill University, Quebec, H3A 2B4, Montreal, Canada.
Neuroscience. 2000;100(4):769-75. doi: 10.1016/s0306-4522(00)00316-x.
Neuronal nitric oxide synthase and haem oxygenase-2 are postulated to be important enzymes involved in neuronal transmission and modulation of free radical levels in neurons. Hippocampal and cortical neuronal nitric oxide synthase and haem oxygenase-2 expressions were compared in young adult (6 months) and aged (24-26 months) Long-Evans rats. Aged rats were assigned as either cognitively unimpaired or impaired based on their performances in the Morris 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 impaired animals showed significantly higher neuronal nitric oxide synthase messenger RNA expression than aged cognitively unimpaired animals in several brain regions. For haem oxygenase-2 mRNA expressions, both young and aged cognitively impaired rats showed increased expressions in hippocampi compared with aged cognitively unimpaired rats, while no difference was found in cortices between all three animal groups. The increase in neuronal nitric oxide synthase messenger RNA expression levels in the aged animals may be related 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 age-related changes in neuronal functions. Regarding cognitive status, aged cognitively impaired rats showed significant spatial memory deficits relative 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 memory processes.
据推测，神经元型一氧化氮合酶和血红素加氧酶-2是参与神经元传递和调节神经元自由基水平的重要酶。比较了年轻成年（6个月）和老年（24 - 26个月）的Long-Evans大鼠海马和皮质中神经元型一氧化氮合酶和血红素加氧酶-2的表达。根据老年大鼠在莫里斯水迷宫行为任务中的表现，将其分为认知未受损或受损组。原位杂交显示，老年大鼠海马和皮质的选定区域中神经元型一氧化氮合酶信使核糖核酸水平升高。此外，在几个脑区中，老年认知受损动物的神经元型一氧化氮合酶信使核糖核酸表达明显高于老年认知未受损动物。对于血红素加氧酶-2信使核糖核酸的表达，与老年认知未受损大鼠相比，年轻和老年认知受损大鼠的海马表达均增加，而三组动物的皮质中未发现差异。老年动物中神经元型一氧化氮合酶信使核糖核酸表达水平的增加可能与衰老过程中自由基产生增加有关。或者，神经元型一氧化氮合酶和血红素加氧酶-2信使核糖核酸表达升高可能代表对氧化应激和神经元功能与年龄相关变化的代偿反应。关于认知状态，老年认知受损大鼠相对于年轻和老年认知未受损大鼠表现出明显的空间记忆缺陷。我们的数据表明，在涉及学习和记忆过程的脑区中，与年龄相关的认知障碍与神经元型一氧化氮合酶和血红素加氧酶-2系统的信使核糖核酸表达变化之间存在相关性。
