PTEN INHIBITION PREVENTS RAT CORTICAL NEURON INJURY AFTER HYPDXIA-ISCHEMIA

被引：46
作者：
Zhao, J. [1 ,2 ]
Qu, Y. [1 ,2 ]
Wu, J. [1 ,2 ]
Cao, M. [2 ]
Ferriero, D. M. [3 ]
Zhang, L. [1 ,2 ]
Mu, D. [1 ,2 ,3 ]
机构：
[1] Sichuan Univ, West China Univ Hosp 2, Dept Pediat, Chengdu 610041, Sichuan, Peoples R China
[2] Sichuan Univ, Minist Educ, Key Lab Obstet & Gynecol & Pediat Dis & Birth Def, Chengdu 610041, Sichuan, Peoples R China
[3] Univ Calif San Francisco, Dept Pediat & Neurol, San Francisco, CA 94143 USA
来源：
NEUROSCIENCE | 2013年 / 238卷
基金：
美国国家科学基金会;
关键词：
neuron; hypoxia-ischemia; signaling pathway; PTEN; GSK-3; beta; CRMP-2; POLARITY; BRAIN; PHOSPHORYLATION; ESTABLISHMENT; INVOLVEMENT; PHOSPHATASE; MECHANISMS; GSK-3-BETA; PATHWAY; CRMP-2;
D O I：
10.1016/j.neuroscience.2013.02.046
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Alterations in axon-dendrite polarity impair functional recovery in the developing CNS after hypoxia-ischemia (HI) injury. PTEN (phosphatase and tensin homolog deleted on chromosome 10) signaling pathway mediates the formation of neuronal polarity. However, its role in cerebral HI injury is not fully understood. In this study, we investigated the role of PTEN pathway in regulation of axon-dendrite polarity using an oxygen-glucose deprivation (OGD) model with rat cortical neurons. We found that the activity of PTEN and glycogen synthase kinase 313 (GSK-3 beta) was increased after OGD, along with the decrease of the activity in protein kinase B (Akt) and collapsin response mediator protein-2 (CRMP-2). Pretreatment with bpv, a potent inhibitor of PTEN, caused a decrease of the activity in PTEN and GSK-3 beta, and a significant increase of the activity in Akt and CRMP-2. Simultaneously, the morphological polarity of neurons was maintained and neuronal apoptosis was reduced. Moreover, inhibition of PTEN rescued vesicle recycling in axons. These findings suggested that the PTEN/Akt/GSK-3 beta/CRMP-2 pathway is involved in the regulation of axon-dendrite polarity, providing a novel route for protecting neurons following neonatal HI. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码：242 / 251
页数：10
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