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Open Access 01-02-2016 | Original Paper

Neuroinflammation impairs adaptive structural plasticity of dendritic spines in a preclinical model of Alzheimer’s disease

Authors: Chengyu Zou, Yuan Shi, Jasmin Ohli, Ulrich Schüller, Mario M. Dorostkar, Jochen Herms

Published in: Acta Neuropathologica | Issue 2/2016

Abstract

To successfully treat Alzheimer’s disease (AD), pathophysiological events in preclinical stages need to be identified. Preclinical AD refers to the stages that exhibit amyloid deposition in the brain but have normal cognitive function, which are replicated in young adult APPswe/PS1deltaE9 (deltaE9) mice. By long-term in vivo two-photon microscopy, we demonstrate impaired adaptive spine plasticity in these transgenic mice illustrated by their failure to increase dendritic spine density and form novel neural connections when housed in enriched environment (EE). Decrease of amyloid plaques by reducing BACE1 activity restores the gain of spine density upon EE in deltaE9 mice, but not the remodeling of neural networks. On the other hand, anti-inflammatory treatment with pioglitazone or interleukin 1 receptor antagonist in deltaE9 mice successfully rescues the impairments in increasing spine density and remodeling of neural networks during EE. Our data suggest that neuroinflammation disrupts experience-dependent structural plasticity of dendritic spines in preclinical stages of AD.

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Title: Neuroinflammation impairs adaptive structural plasticity of dendritic spines in a preclinical model of Alzheimer’s disease
Authors: Chengyu Zou
Yuan Shi
Jasmin Ohli
Ulrich Schüller
Mario M. Dorostkar
Jochen Herms
Publication date: 01-02-2016
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 2/2016
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-015-1527-8

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Neuroinflammation impairs adaptive structural plasticity of dendritic spines in a preclinical model of Alzheimer’s disease

Abstract

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Abstract

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