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前脑特异性敲除PDK1会导致皮层发育过程中的神经元丢失及细胞凋亡增加。

Conditional Deletion of PDK1 in the Forebrain Causes Neuron Loss and Increased Apoptosis during Cortical Development.

作者信息

Xu Congyu, Yu Linjie, Hou Jinxing, Jackson Rosemary J, Wang He, Huang Chaoli, Liu Tingting, Wang Qihui, Zou Xiaochuan, Morris Richard G, Spires-Jones Tara L, Yang Zhongzhou, Yin Zhenyu, Xu Yun, Chen Guiquan

机构信息

State Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center, Ministry of Education (MOE) Key Laboratory of Model Animal for Disease Study, Nanjing University, Nanjing, China.

Department of Neurology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.

出版信息

Front Cell Neurosci. 2017 Oct 20;11:330. doi: 10.3389/fncel.2017.00330. eCollection 2017.

Abstract

Decreased expression but increased activity of PDK1 has been observed in neurodegenerative disease. To study function of PDK1 in neuron survival during cortical development, we generate forebrain-specific conditional knockout (cKO) mice. We demonstrate that cKO mice display striking neuron loss and increased apoptosis. We report that cKO mice exhibit deficits on several behavioral tasks. Moreover, cKO mice show decreased activities for Akt and mTOR. These results highlight an essential role of endogenous PDK1 in the maintenance of neuronal survival during cortical development.

摘要

在神经退行性疾病中已观察到丙酮酸脱氢酶激酶1(PDK1)的表达降低但活性增加。为了研究PDK1在皮质发育过程中神经元存活中的功能,我们构建了前脑特异性条件性敲除(cKO)小鼠。我们证明cKO小鼠表现出明显的神经元丢失和凋亡增加。我们报告cKO小鼠在多项行为任务上存在缺陷。此外,cKO小鼠的Akt和mTOR活性降低。这些结果突出了内源性PDK1在皮质发育过程中维持神经元存活的重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41d3/5655024/e814a36bda91/fncel-11-00330-g001.jpg

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