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Neurobiol Aging. 2018 Dec 6;75:198-208. doi: 10.1016/j.neurobiolaging.2018.11.023. [Epub ahead of print]

CIP2A-promoted astrogliosis induces AD-like synaptic degeneration and cognitive deficits.

Author information

1
Department of Pathophysiology, Key Laboratory of Ministry of Education for Neurological Disorders, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
2
Department of Biology, Boston University, Boston, USA.
3
Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland.
4
Department of Pathophysiology, Key Laboratory of Ministry of Education for Neurological Disorders, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China. Electronic address: rong.liu@hust.edu.cn.

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.

KEYWORDS:

CIP2A; Cognitive deficit; Reactive astrogliosis; Synaptic degeneration

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