Long Term Running Biphasically Improves Methylglyoxal-Related Metabolism, Redox Homeostasis and Neurotrophic Support within Adult Mouse Brain Cortex
Long Term Running Biphasically Improves Methylglyoxal-Related Metabolism, Redox Homeostasis and Neurotrophic Support within Adult Mouse Brain Cortex
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DOI：
10.1371/journal.pone.0031401
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发表时间：
2012-02-08
期刊：
影响因子：
3.7
通讯作者：
Amicarelli, Fernanda
中科院分区：
文献类型：
--
作者：
Falone, Stefano;D'Alessandro, Antonella;Amicarelli, Fernanda
氧化应激和神经营养支持的下降似乎是至关重要的参与脑老化。越来越多的证据表明，促氧化剂甲基乙二醛（MG）是中枢神经系统内与年龄相关的二羰基应激和分子损伤的关键参与者。虽然运动促进活性氧的过量产生，但习惯性运动可能通过激素适应延缓细胞衰老并减少年龄依赖性认知衰退，但运动有益作用的分子机制仍不清楚。特别是，而在青年开始的运动诱导的适应性反应已被广泛研究，慢性和适度的运动开始在成年人的年龄对哺乳动物大脑的非常早期衰老的生化标志的影响还没有得到广泛的研究。本研究调查了成年后开始的长期、强迫和适度跑步是否会影响CD 1雌性小鼠皮质中氧化还原相关的特征和氧化/MG依赖性分子损伤模式之间的相互作用;此外，我们还调查了运动对脑源性神经营养因子（BDNF）依赖性通路活性的可能影响。我们的研究结果表明，在几乎所有研究参数的短暂不平衡之后，后期启动的运动方案通过增强主要ROS和MG靶向清除系统的活性，以及通过保留BDNF依赖的信号传导，通过从成年到中年的过渡，强烈降低了成年小鼠大脑中的分子损伤概况。
Oxidative stress and neurotrophic support decline seem to be crucially involved in brain aging. Emerging evidences indicate the pro-oxidant methylglyoxal (MG) as a key player in the age-related dicarbonyl stress and molecular damage within the central nervous system. Although exercise promotes the overproduction of reactive oxygen species, habitual exercise may retard cellular aging and reduce the age-dependent cognitive decline through hormetic adaptations, yet molecular mechanisms underlying beneficial effects of exercise are still largely unclear. In particular, whereas adaptive responses induced by exercise initiated in youth have been broadly investigated, the effects of chronic and moderate exercise begun in adult age on biochemical hallmarks of very early senescence in mammal brains have not been extensively studied. This research investigated whether a long-term, forced and moderate running initiated in adult age may affect the interplay between the redox-related profile and the oxidative-/MG-dependent molecular damage patterns in CD1 female mice cortices; as well, we investigated possible exercise-induced effects on the activity of the brain derived neurotrophic factor (BDNF)-dependent pathway. Our findings suggested that after a transient imbalance in almost all parameters investigated, the lately-initiated exercise regimen strongly reduced molecular damage profiles in brains of adult mice, by enhancing activities of the main ROS- and MG-targeting scavenging systems, as well as by preserving the BDNF-dependent signaling through the transition from adult to middle age.