Integrin-linked Kinase is Essential for Environmental Enrichment Enhanced Hippocampal Neurogenesis and Memory.
Integrin-linked Kinase is Essential for Environmental Enrichment Enhanced Hippocampal Neurogenesis and Memory.
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整合素连接激酶对于环境丰富增强海马神经发生和记忆至关重要
DOI：
10.1038/srep11456
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发表时间：
2015-06-22
影响因子：
4.6
通讯作者：
Chen ZY
中科院分区：
文献类型：
--
作者：
Xu XF;Li T;Wang DD;Chen B;Wang Y;Chen ZY
丰富的环境对大脑结构和功能有多种影响。脑源性神经营养因子（BDNF）在EE诱导的海马神经发生和记忆增强中是必不可少的。然而，BDNF下游调节EE效应的细胞内途径知之甚少。在这里，我们表明，整合素连接激酶（ILK）水平升高EE刺激后，在BDNF依赖的方式。使用ILK-shRNA（siILK）慢病毒，我们证明ILK的敲低通过增加糖原合成酶激酶-3 β（GSK 3 β）活性损害EE促进的海马神经发生和记忆。最后，在海马中过表达ILK可以挽救BDNF+/−小鼠的神经发生和记忆缺陷。这些结果表明ILK通过调节GSK 3 β活性在BDNF介导的海马神经发生和EE刺激后的记忆增强中是不可或缺的。这是对EE增强记忆过程的确切机制的新见解，ILK是值得进一步研究的潜在重要治疗靶点。
Environment enrichment (EE) has a variety of effects on brain structure and function. Brain-derived neurotrophic factor (BDNF) is essential for EE-induced hippocampal neurogenesis and memory enhancement. However, the intracellular pathway downstream of BDNF to modulate EE effects is poorly understood. Here we show that integrin-linked kinase (ILK) levels are elevated upon EE stimuli in a BDNF-dependent manner. Using ILK-shRNA (siILK) lentivirus, we demonstrate that knockdown of ILK impairs EE-promoted hippocampal neurogenesis and memory by increasing glycogen synthase kinase-3β (GSK3β) activity. Finally, overexpressing ILK in the hippocampus could rescue the neurogenesis and memory deficits in BDNF+/−mice. These results indicate that ILK is indispensable for BDNF-mediated hippocampal neurogenesis and memory enhancement upon EE stimuli via regulating GSK3β activity. This is a new insight of the precise mechanism in EE-enhanced memory processes and ILK is a potentially important therapeutic target that merits further study.
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影响因子：
5.3
作者：
Ickes, BR;Pham, TM;Granholm, AC
通讯作者：
Granholm, AC
影响因子：
3.5
作者：
Fuster-Matanzo, Almudena;Llorens-Martin, Maria;Hernandez, Felix
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通讯作者：
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影响因子：
16.2
作者：
Bednarek, Ewa;Caroni, Pico
通讯作者：
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