James Bronwen M, Li Qin, Luo Lizhu, Kendrick Keith M
Key Laboratory for NeuroInformation of Ministry of Education, Center for Information in Medicine, University of Electronic Science and Technology of China Chengdu, Sichuan, China ; Department of Medicine, St Bernard's Hospital Gibraltar, UK.
Key Laboratory for NeuroInformation of Ministry of Education, Center for Information in Medicine, University of Electronic Science and Technology of China Chengdu, Sichuan, China.
Front Cell Neurosci. 2015 Mar 27;9:105. doi: 10.3389/fncel.2015.00105. eCollection 2015.
There is evidence for both neurotoxic and neuroprotective roles of nitric oxide (NO) in the brain and changes in the expression of the neuronal isoform of NO synthase (nNOS) gene occur during aging. The current studies have investigated potential support for either a neurotoxic or neuroprotective role of NO derived from nNOS in the context of aging by comparing olfactory learning and locomotor function in young compared to old nNOS knockout (nNOS(-/-)) and wildtype control mice. Tasks involving social recognition and olfactory conditioning paradigms showed that old nNOS(-/-) animals had improved retention of learning compared to similar aged wildtype controls. Young nNOS(-/-) animals showed superior reversal learning to wildtypes in a conditioned learning task, although their performance was weakened with age. Interestingly, whereas young nNOS(-/-) animals were impaired in long term memory for social odors compared to wildtype controls, in old animals this pattern was reversed, possibly indicating beneficial compensatory changes influencing olfactory memory may occur during aging in nNOS(-/-) animals. Possibly such compensatory changes may have involved increased NO from other NOS isoforms since the memory deficit in young nNOS(-/-) animals could be rescued by the NO-donor, molsidomine. Both nNOS(-/-) and wildtype animals showed an age-associated decline in locomotor activity although young nNOS(-/-) animals were significantly more active than wildtypes, possibly due to an increased interest in novelty. Overall our findings suggest that lack of NO release via nNOS may protect animals to some extent against age-associated cognitive decline in memory tasks typically involving olfactory and hippocampal regions, but not against declines in reversal learning or locomotor activity.
有证据表明一氧化氮（NO）在大脑中具有神经毒性和神经保护作用，并且在衰老过程中，神经元型一氧化氮合酶（nNOS）基因的表达会发生变化。目前的研究通过比较年轻与年老的nNOS基因敲除（nNOS(-/-)）小鼠和野生型对照小鼠的嗅觉学习和运动功能，探讨了衰老背景下nNOS衍生的NO的神经毒性或神经保护作用的潜在支持。涉及社会识别和嗅觉条件反射范式的任务表明，与同龄野生型对照相比，年老的nNOS(-/-)动物在学习记忆方面有所改善。年轻的nNOS(-/-)动物在条件学习任务中表现出比野生型更好的逆向学习能力，尽管它们的表现会随着年龄的增长而减弱。有趣的是，与野生型对照相比，年轻的nNOS(-/-)动物在社会气味的长期记忆方面受损，而在年老动物中这种模式则相反，这可能表明在nNOS(-/-)动物衰老过程中可能发生了影响嗅觉记忆的有益代偿性变化。可能这种代偿性变化涉及其他NOS同工型产生的NO增加，因为年轻nNOS(-/-)动物的记忆缺陷可以被NO供体吗多明挽救。nNOS(-/-)和野生型动物都表现出与年龄相关的运动活动下降，尽管年轻的nNOS(-/-)动物比野生型明显更活跃，这可能是由于对新奇事物的兴趣增加。总体而言，我们的研究结果表明，缺乏通过nNOS释放的NO可能在一定程度上保护动物免受通常涉及嗅觉和海马区域的记忆任务中与年龄相关的认知衰退，但不能防止逆向学习或运动活动的下降。
