重磅!Science揭秘:运动可以促进大脑神经再生,延缓老年痴呆
2018/09/11
我们常常为了减肥狠下心在健身房挥汗如雨。殊不知,这一行动或许还可以帮助我们预防大脑衰退!顶尖期刊《Science》最新发表一篇文章揭示,运动可以促进大脑神经新生,从而有助于改善大脑认知功能。


图片来源:Pixabay

“运动有益健康”——这句简单的口号背后有着大大的科学道理。

9月7日,《Science》发表了一篇题为“Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model”的文章,揭示了“运动延缓老年痴呆”背后的机制。

来自于麻省总医院的科学家们以患有阿尔兹海默症(AD)的小鼠为模型发现,一种能够促进大脑新生神经并保护它们免受损伤的治疗方法,可以模拟运动在防止记忆衰退方面的积极效果,从而改善大脑认知能力。


DOI: 10.1126/science.aan8821

这是否意味着,未来,我们或许可以把运动“装进”药丸里,用于防治老年痴呆?如果是这样,这个“药丸”里应该有哪些分子?Science这篇最新研究给出了线索:

运动延缓大脑衰老?

许多大型研究曾表明,坚持运动可以降低日后记忆缺陷的风险。

2018年4月,一项为期40年、针对超1000名瑞典女性的研究表明,心肺适能较高(“high” cardiovascular fitness,心肺适能较佳可以使我们运动持续较久、且不致于很快疲倦)的人,发生痴呆的时间平均延迟9.5年。这项研究发表在《Neurology》期刊上。

但是这类研究并不能排除其他有可能影响痴呆风险的因素,包括基因以及其他关联健康的生活方式。而且,这项研究也没有揭示运动对于大脑的实际作用。

运动是否有助于AD患者?

对于AD患者,运动是否有助于抵抗病情恶化?相比于人类,啮齿动物更有说服力——在以AD小鼠为模型的研究中,小鼠运动能够降低大脑中累积的蛋白病斑。

现在,《Science》期刊上这篇最新研究表明,相比于久坐不动,经常运动的患病小鼠在一系列记忆测试中表现更好。

但是,多项围绕痴呆老年人(包括AD患者)的“运动研究”却显示出矛盾的结果,只有一部分证据表明,运动可以改善认知能力。而且,这引出一个问题:一旦发生AD等痴呆症后,运动究竟对大脑有多大的好处?

运动对大脑有什么保护作用?

我们知道,运动的一个主要好处是可以帮助大脑产生新的神经元。而海马体是大脑中学习、记忆的关键区域,其中有负责生成新细胞的神经祖细胞。最近,学术界对“关于人类一生中是否能够产生新的神经元”这一话题存在争议。

事实上,对啮齿动物的研究表明,成年后的神经形成有助于保持某些敏锐的认知技能。一些啮齿类动物的研究已经将定期运动与神经发生联系起来,例如让小鼠在轮子上奔跑,似乎可以让大脑中存活的新生海马神经元数量翻倍。

这项新研究中,在记忆测试中表现良好的运动小鼠,同样也被检测出神经发生。


图片来源:CC0 Public Domain

如果不运动,神经发生对大脑有帮助吗?

那么我们是否可以通过其他治疗措施促进神经生成,从而模拟“运动”效果呢?科学家们发现,并没有那么简单——仅仅促进神经发生可能还不够。

他们发现,运动还有助于提高脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)蛋白的水平。这一因子可以促进神经生成,减少患病大脑的炎症。

最新研究表明,小鼠虽然产生了新的脑细胞,但是似乎记忆并没有改善。只有当它们接受额外的基因治疗——添加一种提高BDNF蛋白水平的基因,它们才会在记忆测试中赢过其他未治疗的对照组小鼠。

波士顿哈佛医学院(Harvard Medical School)的神经遗传学家Rudolph Tanzi表示,研究结果表明,在生命早期生成新的神经元可能有助于在日后保护记忆,但是对于已经有阿尔兹海默症的大脑来说,这是“一个充满敌意的游戏环境”,而BDNF蛋白可以负责清理“环境”,以确保新生的神经元能够存活下来。

我们能否用类似的方法治疗老年痴呆症?

相比于减少淀粉样蛋白病斑,医药公司对以上这种方法关注较少。但是一些学者认为,它值得进一步研究。

国家老龄化研究所的神经学家Mark Mattson则认为,这一方法仍然有重要的疑点:

首先,海马体区域的神经祖细胞是空间学习、记忆的关键神经元,但是与阿尔兹海默症患者海马区神经衰退、死亡的神经元不同;

其次,即便通过促进这些新细胞生成保护大脑的某些功能,海马体之外的其他大脑区域依然会受到阿尔兹海默症的影响。

不过,他补充说,这种方法是值得进一步研究的。“到目前为止,关注于淀粉样蛋白一直是一个狭隘的观点。在我看来,方法越多越好。”

责编:悠然

参考资料:

How does exercise keep your brain young?

Study shows how exercise generates new neurons, improves cognition in Alzheimer's mouse

Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model

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  • Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model

    INTRODUCTION Alzheimer’s disease (AD) is the most common form of age-related dementia, characterized by cognitive impairment, neurodegeneration, β-amyloid (Aβ) deposition, neurofibrillary tangle formation, and neuroinflammation. The most popular therapeutic approach aimed at reducing Aβ burden has not yet proved effective in halting disease progression. A successful therapy would both remove the pathological hallmarks of the disease and provide some functional recovery. The hippocampus contains neural progenitor cells that continue to generate new neurons, a process called adult hippocampal neurogenesis (AHN). AHN is impaired before the onset of classical AD pathology in AD mouse models. Human AHN has also been reported to be altered in AD patients. However, evidence supporting a role for AHN in AD has remained sparse and inconclusive. RATIONALE Two fundamental questions remain: (i) whether AHN could be enhanced and exploited for therapeutic purposes for AD, and (ii) whether AHN impairment mediates aspects of AD pathogenesis. To address these questions, we increased AHN genetically (WNT3) and pharmacologically (P7C3) in AD transgenic 5×FAD mice and explored whether promoting AHN alone can ameliorate AD pathology and behavioral symptoms. We assessed the role of exercise, a known neurogenic stimulus, and explored whether promoting AHN in conjunction with the salutary biochemical changes induced by exercise can improve AD pathology and behavioral symptoms in mice. We also investigated whether AHN suppression, by irradiation, temozolomide, or dominant-negative WNT, contributes to AD pathogenesis and assessed the functional roles of AHN in AD. RESULTS Inducing AHN alone conferred minimal to no benefit for improving cognition in 5×FAD mice. Exercise-induced AHN improved cognition along with reduced Aβ load and increased levels of brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), fibronectin type III domain–containing protein–5 (FNDC5), and synaptic markers. However, AHN activation was also required for exercise-induced improvement in memory. Inducing AHN genetically and pharmacologically in combination with elevating BDNF levels mimicked beneficial effects of exercise on AD mice. Conversely, suppressing AHN in early stages of AD exacerbated neuronal vulnerability in later stages of AD, leading to cognitive impairment and increased neuronal loss. However, no such effects from AHN ablation were observed in nontransgenic wild-type (WT) mice, suggesting that AHN has a specific role in AD. CONCLUSION Promoting AHN can only ameliorate AD pathology and cognitive deficits in the presence of a healthier, improved local brain environment, e.g., stimulated by exercise. Increasing AHN alone combined with overexpression of BDNF could mimic exercise-induced improvements in cognition, without reducing Aβ burden. Adult-born neurons generated very early in life are critical for maintaining hippocampal neuronal populations in the hostile brain environment created by AD later in life. Thus, AHN impairment may be a primary event that later mediates other aspects of AD pathogenesis. Future attempts to create pharmacological mimetics of the benefits of exercise on both increased AHN and BDNF may someday provide an effective means for improving cognition in AD. Moreover, increasing neurogenesis in the earliest stages of AD pathogenesis may protect against neuronal cell death later in the disease, providing a potentially powerful disease-modifying treatment strategy for AD.

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