APP Family Regulates Neuronal Excitability and Synaptic Plasticity but Not Neuronal Survival.
APP Family Regulates Neuronal Excitability and Synaptic Plasticity but Not Neuronal Survival.
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DOI：
10.1016/j.neuron.2020.08.011
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发表时间：
2020-11-25
期刊：
影响因子：
16.2
通讯作者：
Shen J
中科院分区：
文献类型：
--
作者：
Lee SH;Kang J;Ho A;Watanabe H;Bolshakov VY;Shen J
淀粉样前体蛋白（APP）与家族性和散发性阿尔茨海默病有关。尽管其重要性，APP家族在神经元功能和存活中的作用仍然不清楚，由于缺乏所有三个APP家族成员的敲除小鼠表现出的围产期致死性。在这里，我们报告说，选择性灭活APP家族成员在兴奋性神经元的出生后前脑的结果既不皮质神经变性，也不增加细胞凋亡和胶质细胞增生到2岁。然而，海马突触可塑性，学习和记忆在这些突变小鼠受损。此外，缺乏APP家族的海马神经元表现出过度兴奋性，这一点可以通过响应去极化电流注射的神经元尖峰增加来证明，而Kv 7通道的阻断则模拟并在很大程度上阻断了APP家族失活的影响。这些结果表明，APP家族不是神经元存活所必需的，并且表明APP家族可能通过Kv7通道调节神经元兴奋性。尽管淀粉样前体蛋白在阿尔茨海默病中的重要性，但它是否支持大脑皮层中神经元在衰老过程中的存活仍不清楚。Lee等人表明淀粉样前体蛋白家族对于神经元存活是必需的，但对于调节神经元兴奋性和突触可塑性是必需的。
Amyloid precursor protein (APP) is associated with both familial and sporadic forms of Alzheimer’s disease. Despite its importance, the role of APP family in neuronal function and survival remains unclear due to perinatal lethality exhibited by knockout mice lacking all three APP family members. Here we report that selective inactivation of APP family members in excitatory neurons of the postnatal forebrain results in neither cortical neurodegeneration nor increases in apoptosis and gliosis up to ~2 years of age. However, hippocampal synaptic plasticity, learning and memory are impaired in these mutant mice. Furthermore, hippocampal neurons lacking APP family exhibit hyperexcitability, as evidenced by increased neuronal spiking in response to depolarizing current injections, whereas blockade of Kv7 channels mimics and largely occludes the effects of APP family inactivation. These findings demonstrate that APP family is not required for neuronal survival, and suggest that APP family may regulate neuronal excitability through Kv7 channels. Despite the importance of the amyloid precursor protein in Alzheimer’s disease, it remains unclear whether it supports neuronal survival in the cerebral cortex during aging. Lee et al. show that the amyloid precursor protein family is dispensable for neuronal survival but is required for regulating neuronal excitability and synaptic plasticity.
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影响因子：
3.3
作者：
LORENT, K;OVERBERGH, L;VANDENBERGHE, H
通讯作者：
VANDENBERGHE, H
DOI：
10.1016/s0006-291x(84)80190-4
发表时间：
1984-01-01
影响因子：
3.1
作者：
GLENNER, GG;WONG, CW
通讯作者：
WONG, CW
影响因子：
56.9
作者：
LEVYLAHAD, E;WASCO, W;TANZI, RE
通讯作者：
TANZI, RE
影响因子：
30.8
作者：
Charlier, C;Singh, NA;Leppert, M
通讯作者：
Leppert, M
影响因子：
56.9
作者：
Biervert, C;Schroeder, BC;Steinlein, OK
通讯作者：
Steinlein, OK