Apolipoprotein E4 Causes Age-Dependent Disruption of Slow Gamma Oscillations during Hippocampal Sharp-Wave Ripples.
Apolipoprotein E4 Causes Age-Dependent Disruption of Slow Gamma Oscillations during Hippocampal Sharp-Wave Ripples.
复制标题
DOI：
10.1016/j.neuron.2016.04.009
复制
发表时间：
2016-05-18
期刊：
影响因子：
16.2
通讯作者：
Huang, Yadong
中科院分区：
文献类型：
--
作者：
Gillespie, Anna K.;Jones, Emily A.;Lin, Yuan-Hung;Karlsson, Mattias P.;Kay, Kenneth;Yoon, Seo Yeon;Tong, Leslie M.;Nova, Philip;Carr, Jessie S.;Frank, Loren M.;Huang, Yadong
载脂蛋白（apo） E4是阿尔茨海默病（AD）的主要遗传危险因素，但其导致认知能力下降的机制尚不清楚。在敲入（KI）小鼠中，人类apoE4导致年龄依赖性学习和记忆障碍以及海马齿状回gaba能中间神经元的退化。在这里，我们报告了两种功能性apoE4-KI表型，涉及锐波涟漪（SWRs），海马网络事件对记忆过程至关重要。老年apoE4-KI小鼠的swr比apoE3-KI小鼠少，并且在swr期间显著降低慢伽马活动。消除gaba能中间神经元中的apoE4，可以防止学习和记忆障碍，挽救老龄小鼠SWR相关的慢伽马活动，但不能挽救SWR的丰富度。在年轻和老年apoE4-KI小鼠中，SWR丰度相似地降低；然而，完全与swr相关的慢伽马缺陷仅在老年apoE4-KI小鼠中出现。这些结果表明，在swr期间，中间神经元激活的慢伽马活动的逐渐下降对apoe4介导的学习和记忆障碍至关重要。
Apolipoprotein (apo) E4 is the major genetic risk factor for Alzheimer’s disease (AD), but the mechanism by which it causes cognitive decline is unclear. In knock-in (KI) mice, human apoE4 causes age-dependent learning and memory impairments and degeneration of GABAergic interneurons in the hippocampal dentate gyrus. Here we report two functional apoE4-KI phenotypes involving sharp-wave ripples (SWRs), hippocampal network events critical for memory processes. Aged apoE4-KI mice had fewer SWRs than apoE3-KI mice and significantly reduced slow gamma activity during SWRs. Elimination of apoE4 in GABAergic interneurons, which prevents learning and memory impairments, rescued SWR-associated slow gamma activity but not SWR abundance in aged mice. SWR abundance was reduced similarly in young and aged apoE4-KI mice; however, the full SWR-associated slow gamma deficit emerged only in aged apoE4-KI mice. These results suggest that progressive decline of interneuron-enabled slow gamma activity during SWRs critically contributes to apoE4-mediated learning and memory impairments.
登录
查看更多内容
影响因子：
16.2
作者：
Carr MF;Karlsson MP;Frank LM
通讯作者：
Frank LM
影响因子：
4.2
作者：
Beydoun MA;Boueiz A;Abougergi MS;Kitner-Triolo MH;Beydoun HA;Resnick SM;O'Brien R;Zonderman AB
通讯作者：
Zonderman AB
DOI：
10.1523/jneurosci.0033-12.2012
发表时间：
2012-04-04
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Bien-Ly N;Gillespie AK;Walker D;Yoon SY;Huang Y
通讯作者：
Huang Y
影响因子：
25
作者：
Girardeau, Gabrielle;Benchenane, Karim;Zugaro, Michael B.
通讯作者：
Zugaro, Michael B.
影响因子：
2.9
作者：
BUZSAKI, G
通讯作者：
BUZSAKI, G