KCNQ channels regulate age-related memory impairment.
KCNQ channels regulate age-related memory impairment.
复制标题
DOI：
10.1371/journal.pone.0062445
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hodge JJ
中科院分区：
文献类型：
--
作者：
Cavaliere S;Malik BR;Hodge JJ
在人类中，KCNQ 2/3异聚体通道形成一种M电流，作为神经元兴奋性的制动器，突变导致一种形式的癫痫。在哺乳动物中，M-电流被证明是神经元可塑性的关键调节器，其基础是联想记忆和乙醇反应。先前的研究表明，酒精行为和成瘾变化背后的许多分子和可塑性机制与记忆的分子和可塑性机制相同。我们发现果蝇中的单个KCNQ通道（dKCNQ）在突变时显示出联合短期和长期记忆的减少，蘑菇体α/β神经元中的KCNQ功能是短期记忆所需的。乙醇破坏野生型果蝇的记忆，但在KCNQ无效突变背景中没有，这表明KCNQ可能是乙醇的直接靶点，乙醇的阻断干扰了记忆形成所需的可塑性机制。我们发现，在人类中，果蝇显示与年龄相关的记忆障碍与KCNQ突变记忆缺陷模仿年龄对记忆的影响。KCNQ的表达在衰老的大脑中通常会减少，而KCNQ突变体蘑菇体神经元中的KCNQ过表达可以恢复与年龄相关的记忆障碍。因此，KCNQ是调节年龄依赖性记忆障碍的中枢可塑性分子。
In humans KCNQ2/3 heteromeric channels form an M-current that acts as a brake on neuronal excitability, with mutations causing a form of epilepsy. The M-current has been shown to be a key regulator of neuronal plasticity underlying associative memory and ethanol response in mammals. Previous work has shown that many of the molecules and plasticity mechanisms underlying changes in alcohol behaviour and addiction are shared with those of memory. We show that the single KCNQ channel in Drosophila (dKCNQ) when mutated show decrements in associative short- and long-term memory, with KCNQ function in the mushroom body α/βneurons being required for short-term memory. Ethanol disrupts memory in wildtype flies, but not in a KCNQ null mutant background suggesting KCNQ maybe a direct target of ethanol, the blockade of which interferes with the plasticity machinery required for memory formation. We show that as in humans, Drosophila display age-related memory impairment with the KCNQ mutant memory defect mimicking the effect of age on memory. Expression of KCNQ normally decreases in aging brains and KCNQ overexpression in the mushroom body neurons of KCNQ mutants restores age-related memory impairment. Therefore KCNQ is a central plasticity molecule that regulates age dependent memory impairment.
登录
查看更多内容
影响因子：
16.2
作者：
Miyashita T;Oda Y;Horiuchi J;Yin JC;Morimoto T;Saitoe M
通讯作者：
Saitoe M
DOI：
10.1073/pnas.0609278104
发表时间：
2007-03-06
影响因子：
11.1
作者：
Ocorr, Karen;Reeves, Nick L.;Bodmer, Rolf
通讯作者：
Bodmer, Rolf
影响因子：
16.2
作者：
Ramos, BP;Birnbaum, SG;Arnsten, AFT
通讯作者：
Arnsten, AFT
影响因子：
56.9
作者：
Connolly, JB;Roberts, IJH;OKane, CJ
通讯作者：
OKane, CJ
影响因子：
64.5
作者：
Kubisch, C;Schroeder, BC;Jentsch, TJ
通讯作者：
Jentsch, TJ