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Apolipoprotein E4 Impairs in vivo Hippocampal Long-Term Synaptic Plasticity by Reducing the Phosphorylation of CaMKIIα and CREB
QIAO Feng 1,GAO Xiuping 2,YUAN Li 1,CAI Hongyan 1,QI Jinshun 1 *
1.Department of Physiology, Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan,030001
2. Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA
*Correspondence author
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Funding: Natural Science Foundation of Shanxi Province of China（No.No. 2010-5）, 教育部高等学校博士学科点专项科研基金（No.No. 20101417110001）, National Science Foundation of China （No.No.31271201)Special Foundation for High Schools Doctoral Program of Ministry of Educatio）
Opened online:13 March 2014
Accepted by: none
Citation: QIAO Feng,GAO Xiuping,YUAN Li.Apolipoprotein E4 Impairs in vivo Hippocampal Long-Term Synaptic Plasticity by Reducing the Phosphorylation of CaMKIIα and CREB[OL]. [13 March 2014] http://en.paper.edu.cn/en_releasepaper/content/4588972
 
 
Inheritance of the apolipoprotein E genotype ε4 (APOE4) is a powerful risk factor for most cases of late-onset Alzheimer's disease (AD). However, the effects of apoE4 on the long-term synaptic plasticity and its underlying mechanism have not clearly investigated. In the present study, we examined the effects of apoE4 on hippocampal late-phase long-term potentiation (L-LTP) and investigated its probable molecular mechanisms by using in vivo field potential recording, immunohistochemistry and western blotting. The results showed that: (1) intra-hippocampal injection of 0.2 μg apoE4, but not apoE2, before high frequency stimulations (HFSs) attenuated the induction of hippocampal L-LTP in the CA1 region, while injection of the same concentration of apoE4 after HFSs, even at a higher concentration (2 μg), did not affect the long term synaptic plasticity; (2) apoE4 injection did not affect the paired pulse facilitation (PPF) in the hippocampal CA1 region; (3) apoE4 injection before, not after, HFSs significantly decreased the levels of phospharylated Ca2+/calmodulin-dependent protein kinase II (p-CaMKII) and phospharylated cAMP response element-binding protein (p-CREB) in the hippocampus. These results demonstrated for the first time that apoE4 could impair hippocampal L-LTP by reducing p-CaMKIIα and p-CREB, suggesting that the apoE4-induced suppression of hippocampal long-term synaptic plasticity may contribute to the cognitive impairments in genetic AD; and both CaMKII and CREB are important intracellular targets of the neurotoxic apoE4.
Keywords:apolipoprotein E4 (apoE4); synaptic plasticity; late-phase long-term potentiation (L-LTP); Ca2+/calmodulin-dependent protein kinase II (CaMKII); cAMP response element-binding protein (CREB); hippocampus
 
 
 

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