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Genome-wide RNA sequencing analysis reveals that IGF-2 attenuates memory decline, oxidative stress and amyloid plaques in an Alzheimer’s disease mouse model (AD) by activating the PI3K/AKT/CREB signaling pathway

Published online by Cambridge University Press:  03 July 2019

Lei Xia ,
Xiangyu Zhu ,
Ying Zhao ,
Guang Yang ,
Xiaohua Zuo ,
Peng Xie ,
Chun Chen Open the ORCID record for Chun Chen [Opens in a new window]  and
Qiu Han
Lei Xia
Affiliation:
Department of Neurology, Huai’an First People’s Hospital, the Affiliated Huaian No.1 People’s Hospital ofNanjing Medical University, Huaian, Jiangsu, China
Xiangyu Zhu
Affiliation:
ICU, The Second People’s Hospital of Huaian, Huaian Affiliated Hospital of Xuzhou Medical University, Huaian, Jiangsu, China
Ying Zhao
Affiliation:
Department of Neurology, The Second People’s Hospital of Huaian, the Affiliated Huai’an Hospital of Xuzhou Medical University, Huaian, Jiangsu, China
Guang Yang
Affiliation:
Department of Neurology, The Second People’s Hospital of Huaian, the Affiliated Huai’an Hospital of Xuzhou Medical University, Huaian, Jiangsu, China
Xiaohua Zuo
Affiliation:
Department of Pain Treatment, The Second People’s Hospital of Huaian, the Affiliated Huai’an Hospital of Xuzhou Medical University, Huaian, Jiangsu, China
Peng Xie
Affiliation:
Department of Neurosurgery, The Second People’s Hospital of Huaian, the Affiliated Huai’an Hospital of Xuzhou Medical University, Huaian, Jiangsu, China
Chun Chen*
Affiliation:
Department of Neurology, Hongze Huaian District People’s Hospital, Huaian, Jiangsu, China
Qiu Han*
Affiliation:
Department of Neurology, The Second People’s Hospital of Huaian, the Affiliated Huai’an Hospital of Xuzhou Medical University, Huaian, Jiangsu, China
*
Correspondence should be addressed to: Chun Chen, Department of Neurology, Hongze Huaian District People’s Hospital, No.102 Dongfeng Road, Hongze District, Huaian 223100, Jiangsu, China. Phone: +86 0517-87283416. Email: 1065748391@qq.com.
Qiu Han, Department of Neurology, The Second People’s Hospital of Huaian, the Affiliated Huai’an Hospital of Xuzhou Medical University, No.62 South Huaihai Road, Huaian 223002, Jiangsu, China. Phone: +86 0517-80871771. Email: haqhan@163.com.
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Abstract

Objectives:

Alzheimer’s Disease (AD), characterized by deficits in memory and cognition and by behavioral impairment, is a progressive neurodegenerative disorder that influences more than 47 million people worldwide. Currently, no available drug is able to stop AD progression. Therefore, novel therapeutic strategies need to be investigated.

Measurements:

We analyzed the RNA sequencing data (RNA-seq) derived from the Gene Expression Omnibus (GEO) database to identify the differentially expressed mRNAs in AD. The AD mouse model Tg2576 was used to verify the effects of IGF-2. The Morris Water Maze was administered to test the role of IGF-2 in memory consolidation. In addition, we quantified cell apoptosis by the TUNEL assay. The levels of amyloid plaques and the levels of Aβ40 and Aβ42 in the hippocampus were also determined by immunohistochemistry and ELISA, respectively.

Results:

RNA-seq analysis revealed that IGF-2 was remarkably reduced in AD. The expression of the upstream genes PI3K and AKT and the downstream gene CREB in the PI3K signaling pathway was significantly increased in the hippocampus of Tg2576 mice cells treated with IGF-2. The Morris water maze test showed that IGF-2 improved memory consolidation in Tg2576 mice. The activity of caspase-3 was decreased in Tg2576 mice treated with IGF-2. Amyloid plaques in the hippocampus were reduced, and the levels of Aβ40 and Aβ42 were decreased. The above effects of IGF-2 on AD were blocked when the PI3K signaling pathway inhibitor wortmannin was added.

Conclusions:

IGF-2 attenuates memory decline, oxidative stress, cell apoptosis and amyloid plaques in the AD mouse model Tg2576 by activating the PI3K/AKT/CREB signaling pathway.

Keywords

genome-wide RNA sequencing analysisIGF-2PI3K/AKT/CREBAlzheimer’s disease (AD)
Type
Original Research Article
Information
International Psychogeriatrics , Volume 31 , Issue 7: Issue Theme: Diverse Approaches to Stemming Cognitive Decline , July 2019 , pp. 947 - 959
Copyright
© International Psychogeriatric Association 2019 

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Footnotes

#

These authors contributed equally to this work.

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