A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
CIP2A-promoted astrogliosis induces AD-like synaptic degeneration and cognitive deficits
Tekijät: 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.
Kustantaja: ELSEVIER SCIENCE INC
Julkaisuvuosi: 2019
Journal: Neurobiology of Aging
Tietokannassa oleva lehden nimi: NEUROBIOLOGY OF AGING
Lehden akronyymi: NEUROBIOL AGING
Vuosikerta: 75
Aloitussivu: 198
Lopetussivu: 208
Sivujen määrä: 11
ISSN: 0197-4580
DOI: https://doi.org/10.1016/j.neurobiolaging.2018.11.023
Tiivistelmä
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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