A1 Refereed original research article in a scientific journal
CIP2A-promoted astrogliosis induces AD-like synaptic degeneration and cognitive deficits
Authors: Shentu Y-P., Hu W.T., Zhang Q., Huo Y.D., Liang J.W., Liuyang Z-Y., Zhou H., Wei H., Ke D., Wang X.C., Wang J.Z., Man H.Y., Westermarck J., Liu R.
Publisher: ELSEVIER SCIENCE INC
Publication year: 2019
Journal: Neurobiology of Aging
Journal name in source: NEUROBIOLOGY OF AGING
Journal acronym: NEUROBIOL AGING
Volume: 75
First page : 198
Last page: 208
Number of pages: 11
ISSN: 0197-4580
DOI: https://doi.org/10.1016/j.neurobiolaging.2018.11.023
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 A beta, 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. (C) 2018 Elsevier Inc. All rights reserved.
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 A beta, 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. (C) 2018 Elsevier Inc. All rights reserved.
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