CIP2A-promoted Astrogliosis Induces AD-like Synaptic Degeneration and Cognitive Deficits

Overview

Journal Neurobiol Aging

Publisher Elsevier

Specialties Geriatrics
Neurology
Physiology

Date 2018 Dec 30

PMID 30594047

Citations 12

Authors

Yang-Ping Shentu

Wen-Ting Hu

Qing Zhang

Yuda Huo

Jia-Wei Liang

Zhen-Yu Liuyang

Huan Zhou

Hui Wei

Dan Ke

Xiao-Chuan Wang

Jian-Zhi Wang

Heng-Ye Man

Jukka Westermarck

Rong Liu

Affiliations

Soon will be listed here.

Abstract

Reactive astrogliosis and early synaptic degeneration are 2 characteristic hallmarks in Alzheimer's disease (AD) brains, but a direct link between the 2 events has not been established. Here, we show that cancerous inhibitor of PP2A (CIP2A), a cancerous protein with high expression level in astrocytes, is upregulated in patients with AD and 3xTg-AD transgenic mice. Overexpression of CIP2A in astrocytes through adeno-associated virus infection both in cultured cells and in mice brains results in activation of astrocytes, increased production of cytokines and Aβ, and synaptic degeneration indicated by decreased levels of synaptic proteins, spine loss, and impairment in long-term potentiation. As a result of synaptic degeneration, CIP2A overexpression in astrocytes in vivo induces significant deficits in visual episodic memory detected by novel objective recognition test and spatial memory detected by Morris water maze. We conclude that CIP2A-promoted astrogliosis induces synaptic degeneration and cognitive deficits in AD.

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