Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-β.
Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-β.
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DOI：
10.1038/nn.3356
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发表时间：
2013-05
影响因子：
25
通讯作者：
Mucke, Lennart
中科院分区：
文献类型：
--
作者：
Suberbielle, Elsa;Sanchez, Pascal E.;Kravitz, Alexxai V.;Wang, Xin;Ho, Kaitlyn;Eilertson, Kirsten;Devidze, Nino;Kreitzer, Anatol C.;Mucke, Lennart
我们发现，一个自然的行为，探索一个新的环境，导致DNA双链断裂（DSB）在年轻的成年野生型小鼠的神经元。DSB发生在多个脑区，在参与空间学习和记忆的齿状回中最丰富，并在24小时内修复。通过感觉或光遗传学刺激增加神经元活动增加了相关但不相关网络中的神经元DSB。人类淀粉样前体蛋白（hAPP）转基因小鼠，模拟阿尔茨海默病的关键方面，在基线时增加了神经元DSB，探索后更严重和延长了DSB。抑制异常神经元活动和改善hAPP小鼠记忆的干预使其DSB水平正常化。阻断突触外NMDA型谷氨酸受体可防止神经元培养物中淀粉样蛋白-β（Aβ）诱导的DSB。因此，神经元DSB的短暂增加是生理性脑活动的结果，Aβ很可能通过引发突触功能障碍加剧DNA损伤。
We show that a natural behavior, exploration of a novel environment, causes DNA double-strand breaks (DSBs) in neurons of young adult wildtype mice. DSBs occurred in multiple brain regions, were most abundant in the dentate gyrus, which is involved in spatial learning and memory, and were repaired within 24 hours. Increasing neuronal activity by sensory or optogenetic stimulation increased neuronal DSBs in relevant but not irrelevant networks. Human amyloid precursor protein (hAPP) transgenic mice, 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 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.
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影响因子：
4.2
作者：
Lee HG;Casadesus G;Zhu X;Castellani RJ;McShea A;Perry G;Petersen RB;Bajic V;Smith MA
通讯作者：
Smith MA
通过基础神经节电路的光遗传控制对帕金森运动行为的调节。
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1523/jneurosci.0203-11.2011
发表时间：
2011-05-04
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Li S;Jin M;Koeglsperger T;Shepardson NE;Shankar GM;Selkoe DJ
通讯作者：
Selkoe DJ
影响因子：
3.4
作者：
Crowe, Samantha L.;Movsesyan, Vilen A.;Kondratyev, Alexei
通讯作者：
Kondratyev, Alexei
DOI：
10.1073/pnas.1204156109
发表时间：
2012-09-11
影响因子：
11.1
作者：
Canugovi, Chandrika;Yoon, Jeong Seon;Bohr, Vilhelm A.
通讯作者：
Bohr, Vilhelm A.