与面对新环境一样，一些看似不唐突的经历可以增加小鼠的大脑活动并可导致其神经细胞中的DNA受损，《自然—神经科学》刊登了这一研究结论。该项研究还认为，这种影响在神经退行性疾病中会加大。
Lennart Mucke等人发现，小鼠在经历全新环境时，其大脑中包括齿状回（空间记忆所需要的一个区域）在内的某些区域的神经细胞会产生DNA双链断裂现象。但是，这些断裂的DNA中有许多会通过细胞的DNA修复机制在24小时内得到修复。他们还发现，将神经细胞暴露于β淀粉样蛋白（一种会在阿尔兹海默症病人脑内不断积累的蛋白片段，可能是该病的主要病因）中会增加活跃神经细胞中的DNA双链断裂数。研究人员报告称，通过降低微管稳定蛋白tau的水平浓度或者使用抗癫痫药物levetiracetam的方式来阻断异常的大脑活动可以减少这些活跃神经细胞中DNA双链断裂数的增加。
这项研究的数个结论表明DNA修复机制是在较寻常的大脑活动中保持神经细胞健康和稳定的关键因素，而且暗示了另一种机制的存在——利用该机制，β淀粉样蛋白的积累可以加重神经细胞负担从而可能击败DNA修复机制，并导致神经退化以及相关疾病的产生。（生物谷Bioon.com）
Nature Neuroscience, doi:10.1038/nn.3356
Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-β
Elsa Suberbielle,Pascal E Sanchez,Alexxai V Kravitz,Xin Wang,Kaitlyn Ho,Kirsten Eilertson,Nino Devidze,Anatol C Kreitzer& Lennart Mucke
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We show that a natural behavior, exploration of a novel environment, causes DNA double-strand breaks (DSBs) in neurons of young adult wild-type mice. DSBs occurred in multiple brain regions, were most abundant in the dentate gyrus, which is involved in learning and memory, and were repaired within 24 h. Increasing neuronal activity by sensory or optogenetic stimulation increased neuronal DSBs in relevant but not irrelevant networks. Mice transgenic for human amyloid precursor protein (hAPP), which simulate key aspects of Alzheimer's disease, had increased neuronal DSBs at baseline and more severe and prolonged DSBs after exploration. Interventions that suppress aberrant neuronal activity and improve learning and memory in hAPP mice normalized their levels of DSBs. Blocking extrasynaptic NMDA-type glutamate receptors prevented amyloid-β (Aβ)-induced DSBs in neuronal cultures. Thus, transient increases in neuronal DSBs occur as a result of physiological brain activity, and Aβ exacerbates DNA damage, most likely by eliciting synaptic dysfunction.
