4R Tau Modulates Cocaine-Associated Memory through Adult Dorsal Hippocampal Neurogenesis
4R Tau Modulates Cocaine-Associated Memory through Adult Dorsal Hippocampal Neurogenesis
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4R Tau 通过成人背海马神经发生调节可卡因相关记忆。
DOI：
10.1523/jneurosci.2848-20.2021
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发表时间：
2021-08-04
影响因子：
5.3
通讯作者：
Cen, Xiaobo
中科院分区：
文献类型：
--
作者：
Li, Hongchun;Xu, Wei;Cen, Xiaobo
吸毒成瘾的发育，持久性和复发需要药物给药的药物记忆，这是药物给药的上下文刺激。成年海马神经发生（AHN）有助于可卡因记忆形成。但是，基本机制尚不清楚。在可卡因相关的记忆形成期间，雄性小鼠的海马表达显着降低。小鼠海马中四个微管结合重复tau（4R tau）的遗传过表达通过抑制AHN来破坏可卡因的记忆。此外，4R TAU与磷酸肌醇3-激酶（PI3K）-P85直接相互作用，并损害其核易位和PI3K-AKT信号传导，这是海马神经元增殖所需的过程。总体而言，4R TAU通过破坏AHN来调节可卡因记忆的形成，提出了可卡因记忆形成的一种新型机制，并为可卡因成瘾的治疗提供了新的策略。
The development, persistence and relapse of drug addiction require drug memory that generally develops with drug administration-paired contextual stimuli. Adult hippocampal neurogenesis (AHN) contributes to cocaine memory formation; however, the underlying mechanism remains unclear. Male mice hippocampal expression of Tau was significantly decreased during the cocaine-associated memory formation. Genetic overexpression of four microtubule-binding repeats Tau (4R Tau) in the mice hippocampus disrupted cocaine memory by suppressing AHN. Furthermore, 4R Tau directly interacted with phosphoinositide 3-kinase (PI3K)-p85 and impaired its nuclear translocation and PI3K-AKT signaling, processes required for hippocampal neuron proliferation. Collectively, 4R Tau modulates cocaine memory formation by disrupting AHN, suggesting a novel mechanism underlying cocaine memory formation and provide a new strategy for the treatment of cocaine addiction.