與面對新環(huán)境一樣,，一些看似不唐突的經(jīng)歷可以增加小鼠的大腦活動并可導(dǎo)致其神經(jīng)細胞中的DNA受損，《自然—神經(jīng)科學(xué)》刊登了這一研究結(jié)論,。該項研究還認(rèn)為,，這種影響在神經(jīng)退行性疾病中會加大。
Lennart Mucke等人發(fā)現(xiàn),，小鼠在經(jīng)歷全新環(huán)境時,，其大腦中包括齒狀回（空間記憶所需要的一個區(qū)域）在內(nèi)的某些區(qū)域的神經(jīng)細胞會產(chǎn)生DNA雙鏈斷裂現(xiàn)象,。但是，這些斷裂的DNA中有許多會通過細胞的DNA修復(fù)機制在24小時內(nèi)得到修復(fù),。他們還發(fā)現(xiàn),，將神經(jīng)細胞暴露于β淀粉樣蛋白（一種會在阿爾茲海默癥病人腦內(nèi)不斷積累的蛋白片段，可能是該病的主要病因）中會增加活躍神經(jīng)細胞中的DNA雙鏈斷裂數(shù),。研究人員報告稱,，通過降低微管穩(wěn)定蛋白tau的水平濃度或者使用抗癲癇藥物levetiracetam的方式來阻斷異常的大腦活動可以減少這些活躍神經(jīng)細胞中DNA雙鏈斷裂數(shù)的增加。
這項研究的數(shù)個結(jié)論表明DNA修復(fù)機制是在較尋常的大腦活動中保持神經(jīng)細胞健康和穩(wěn)定的關(guān)鍵因素,，而且暗示了另一種機制的存在——利用該機制,，β淀粉樣蛋白的積累可以加重神經(jīng)細胞負擔(dān)從而可能擊敗DNA修復(fù)機制，并導(dǎo)致神經(jīng)退化以及相關(guān)疾病的產(chǎn)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.
