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

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

Author information

1
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.
2
Department of Neurology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
3
Centre for Cognitive and Neural Systems, University of Edinburgh, Edinburgh, United Kingdom.
4
Consejo Superior de Investigaciones Científicas, Universidad Miguel Hernández, Instituto de Neurociencias, Alicante, Spain.
5
Centre for Dementia Prevention, University of Edinburgh, Edinburgh, United Kingdom.
6
Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh, United Kingdom.
7
Department of Geriatrics, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.

Abstract

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.

KEYWORDS:

Akt; PDK1; apoptosis; learning and memory; mTOR; neuron loss

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