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首页> 外文期刊>BMC Neuroscience >Regional age-related changes in neuronal nitric oxide synthase (nNOS), messenger RNA levels and activity in SAMP8 brain
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Regional age-related changes in neuronal nitric oxide synthase (nNOS), messenger RNA levels and activity in SAMP8 brain

机译：SAMP8脑中神经元一氧化氮合酶（nNOS），信使RNA水平和活性的区域性年龄相关变化

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Background Nitric oxide (NO) is a multifunctional molecule synthesized by three isozymes of the NO synthase (NOSs) acting as a messenger/modulator and/or a potential neurotoxin. In rodents, the role of NOSs in sleep processes and throughout aging is now well established. For example, sleep parameters are highly deteriorated in senescence accelerated-prone 8 (SAMP8) mice, a useful animal model to study aging or age-associated disorders, while the inducible form of NOS (iNOS) is down-regulated within the cortex and the sleep-structures of the brainstem. Evidence is now increasing for a role of iNOS and resulting oxidative stress but not for the constitutive expressed isozyme (nNOS). To better understand the role of nNOS in the behavioural impairments observed in SAMP8 versus SAMR1 (control) animals, we evaluated age-related variations occurring in the nNOS expression and activity and nitritesitrates (NOx-) levels, in three brain areas (n = 7 animals in each group). Calibrated reverse transcriptase (RT) and real-time polymerase chain reaction (PCR) and biochemical procedures were used. Results We found that the levels of nNOS mRNA decreased in the cortex and the hippocampus of 8- vs 2-month-old animals followed by an increase in 12-vs 8-month-old animals in both strains. In the brainstem, levels of nNOS mRNA decreased in an age-dependent manner in SAMP8, but not in SAMR1. Regional age-related changes were also observed in nNOS activity. Moreover, nNOS activity in hippocampus was found lower in 8-month-old SAMP8 than in SAMR1, while in the cortex and the brainstem, nNOS activities increased at 8 months and afterward decreased with age in SAMP8 and SAMR1. NOx- levels showed profiles similar to nNOS activities in the cortex and the brainstem but were undetectable in the hippocampus of SAMP8 and SAMR1. Finally, NOx- levels were higher in the cortex of 8 month-old SAMP8 than in age-matched SAMR1. Conclusion Concomitant variations occurring in NO levels derived from nNOS and iNOS at an early age constitute a major factor of risk for sleep and/or memory impairments in SAMP8.
机译：背景一氧化氮（NO）是由NO合酶（NOS）的三种同工酶合成的多功能分子，这些合酶充当信使/调节剂和/或潜在的神经毒素。在啮齿动物中，NOS在睡眠过程和整个衰老过程中的作用现已被充分确立。例如，在易于衰老的8号（SAMP8）小鼠中，睡眠参数高度恶化，这是研究衰老或与年龄相关的疾病的有用动物模型，而可诱导形式的NOS（iNOS）在皮层和皮层中被下调。脑干的睡眠结构。现在有关iNOS的作用和由此产生的氧化应激的证据正在增加，但对于组成型表达的同工酶（nNOS）则没有。为了更好地了解nNOS在SAMP8与SAMR1（对照）动物中观察到的行为障碍中的作用，我们评估了nNOS表达和活性以及亚硝酸盐/硝酸盐（NOx -）水平中与年龄相关的变异。 ，分布在三个大脑区域（每组n = 7只动物）。使用校准的逆转录酶（RT）和实时聚合酶链反应（PCR）以及生化程序。结果我们发现，两种品系中8个月龄和2个月龄动物的皮质和海马中nNOS mRNA的水平均降低，随后8个月龄的12-vs 8月龄动物的nNOS mRNA的水平升高。在脑干中，SAMP8中nNOS mRNA的水平以年龄依赖性方式降低，而SAMR1中不是。在nNOS活动中也观察到了与年龄相关的区域性变化。此外，发现8个月大的SAMP8中海马的nNOS活性低于SAMR1，而在皮层和脑干中，nAMPS活性在8个月时增加，随后随年龄增长而降低。 NOx -水平在皮质和脑干中显示出与nNOS活性相似的特征，但在SAMP8和SAMR1的海马中未检测到。最后，在8个月大的SAMP8皮层中，NOx -水平高于年龄匹配的SAMR1。结论早年从nNOS和iNOS衍生而来的NO水平的同时变化是构成SAMP8睡眠和/或记忆障碍风险的主要因素。

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