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

Decreased expression but increased activity of PDK1 has been observed in neurodegenerative disease. To study in vivo function of PDK1 in neuron survival during cortical development, we generate forebrain-specific PDK1 conditional knockout (cKO) mice. We demonstrate that PDK1 cKO mice display strikin...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Neuroscience
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655024/
https://www.ncbi.nlm.nih.gov/pubmed/29104535
http://dx.doi.org/10.3389/fncel.2017.00330
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author 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
author_facet 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
author_sort Xu, Congyu
collection PubMed
description Decreased expression but increased activity of PDK1 has been observed in neurodegenerative disease. To study in vivo function of PDK1 in neuron survival during cortical development, we generate forebrain-specific PDK1 conditional knockout (cKO) mice. We demonstrate that PDK1 cKO mice display striking neuron loss and increased apoptosis. We report that PDK1 cKO mice exhibit deficits on several behavioral tasks. Moreover, PDK1 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.
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spelling pubmed-56550242017-11-03 Conditional Deletion of PDK1 in the Forebrain Causes Neuron Loss and Increased Apoptosis during Cortical Development 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 Front Cell Neurosci Neuroscience Decreased expression but increased activity of PDK1 has been observed in neurodegenerative disease. To study in vivo function of PDK1 in neuron survival during cortical development, we generate forebrain-specific PDK1 conditional knockout (cKO) mice. We demonstrate that PDK1 cKO mice display striking neuron loss and increased apoptosis. We report that PDK1 cKO mice exhibit deficits on several behavioral tasks. Moreover, PDK1 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. Frontiers Media S.A. 2017-10-20 /pmc/articles/PMC5655024/ /pubmed/29104535 http://dx.doi.org/10.3389/fncel.2017.00330 Text en Copyright © 2017 Xu, Yu, Hou, Jackson, Wang, Huang, Liu, Wang, Zou, Morris, Spires-Jones, Yang, Yin, Xu and Chen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
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
Conditional Deletion of PDK1 in the Forebrain Causes Neuron Loss and Increased Apoptosis during Cortical Development
title Conditional Deletion of PDK1 in the Forebrain Causes Neuron Loss and Increased Apoptosis during Cortical Development
title_full Conditional Deletion of PDK1 in the Forebrain Causes Neuron Loss and Increased Apoptosis during Cortical Development
title_fullStr Conditional Deletion of PDK1 in the Forebrain Causes Neuron Loss and Increased Apoptosis during Cortical Development
title_full_unstemmed Conditional Deletion of PDK1 in the Forebrain Causes Neuron Loss and Increased Apoptosis during Cortical Development
title_short Conditional Deletion of PDK1 in the Forebrain Causes Neuron Loss and Increased Apoptosis during Cortical Development
title_sort conditional deletion of pdk1 in the forebrain causes neuron loss and increased apoptosis during cortical development
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655024/
https://www.ncbi.nlm.nih.gov/pubmed/29104535
http://dx.doi.org/10.3389/fncel.2017.00330
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