来自斯坦福大学医学院等处的研究人员发表了题为“The ageing systemic milieu negatively regulates neurogenesis and cognitive function”的文章,发现血液中的一种细胞因子成分会促进大脑衰老,这将有助于科学家们更深入的了解衰老的机制。相关成果公布在Nature杂志上。
随着身体变老,大脑会逐渐变迟钝。即使在那些幸免于神经退化性疾病(例如老年痴呆症)的人之中,也很少有新的神经元从大脑的原细胞中再被创造出来,而且已经存在的神经元也会逐渐的变弱。
之前的研究人员以显示给老年鼠注射年轻鼠血液会激发老年鼠的免疫系统和肌肉功能。在这篇文章中,研究人员为了弄清楚这个现象会不会也出现在大脑中。虽然血液大脑界限阻隔了很多血液中的大分子进入大脑,但这层界限不是在所有地方都密封得很好的,这就有机会让某些混合物通过。这些界限在大脑原细胞处尤其密封性的不好,暗示着这些神经元前体也许有机会和循环系统接触。
研究人员分析三个月大的小鼠和大概有两岁大的小鼠的神经形成,然后他们用手术的方法把年轻小鼠和年老小鼠的循环系统连接起来。结果发现年老鼠大脑中的海马体(一种和记忆形成有关的组织)里面的新细胞从少于400个暴涨到将近1000个,而年轻小鼠的新细胞几乎下降了1/4。
而且与年轻的小鼠相比,年老的小鼠在齿状回中具有减少的双肾上腺皮质激素(DCX)阳性神经细胞数量,这意味着神经发生的减少,并在环境恐惧调节和旋臂水迷宫(RAWM)范例中,表现出了依赖海马的学习能力的损伤。
接下来,研究人员利用标准化的复用夹心酶联免疫检测,发现了包括CC趋化因子配体11(CCL11)在内的6种蛋白,这些蛋白在年老未成对小鼠和年轻异时小鼠的血浆中都出现了增加。他们将注意力放在了CCL11上,结果发现这种趋化因子的水平在老年人的血浆和脑脊髓液,以及年老小鼠的血浆中都出现了增加。
这些研究解析了衰老的秘密,下一步研究人员计划着扫描几百个其他因素,来分析还有没有其他因素也对大脑老化起着决定性作用。
原文摘要:
The ageing systemic milieu negatively regulates neurogenesis and cognitive function
In the central nervous system, ageing results in a precipitous decline in adult neural stem/progenitor cells and neurogenesis, with concomitant impairments in cognitive functions1. Interestingly, such impairments can be ameliorated through systemic perturbations such as exercise1. Here, using heterochronic parabiosis we show that blood-borne factors present in the systemic milieu can inhibit or promote adult neurogenesis in an age-dependent fashion in mice. Accordingly, exposing a young mouse to an old systemic environment or to plasma from old mice decreased synaptic plasticity, and impaired contextual fear conditioning and spatial learning and memory. We identify chemokines—including CCL11 (also known as eotaxin)—the plasma levels of which correlate with reduced neurogenesis in heterochronic parabionts and aged mice, and the levels of which are increased in the plasma and cerebrospinal fluid of healthy ageing humans. Lastly, increasing peripheral CCL11 chemokine levels in vivo in young mice decreased adult neurogenesis and impaired learning and memory. Together our data indicate that the decline in neurogenesis and cognitive impairments observed during ageing can be in part attributed to changes in blood-borne factors.