Rosiglitazone Prevents Amyloid-β Oligomer-Induced Impairment Of Synapse Formation And Plasticity Via Increasing Dendrite And Spine Mitochondrial Number

Department

neurobiology

Document Type

Article

Abstract

Rosiglitazone has been known to attenuate neurodegeneration in Alzheimer's disease (AD), but the underlying mechanisms remain to be fully elucidated. In this study, living-cell image, immunocytochemistry, and electrophysiology were used to examine the effects of soluble amyloid-β protein (Aβ) oligomers and rosiglitazone on the synapse formation, plasticity, and mitochondrial distribution in cultured neurons. Incubation of hippocampal cultures with amyloid-β (Aβ) 42 oligomers (0.5 μM) for 3 h significantly decreased dendritic filopodium and synapse density. Pretreatment with rosiglitazone (0.5-5 μM) for 24 h prevented the Aβ 42 - induced loss of dendritic filopodium and synapse in a dose-dependent manner. However, neither Aβ 42 oligomer nor rosiglitazone has a significant effect on the velocity and length of dendritic filopodia. Electrophysiological recording showed that acute exposure of slices with 0.5 μM Aβ 42 oligomers impaired hippocampal long-term potentiation (LTP). Pre-incubation of hippocampal slices with rosiglitazone significantly attenuated the Aβ 42 -induced LTP deficit, which depended on rosiglitazone concentrations (1-5 μM) and pretreatment period (1-5 h). The beneficial effects of rosiglitazone were abolished by the peroxisome proliferator-activated receptor gamma (PPARγ) specific antagonist, GW9662. Moreover, the mitochondrial numbers in the dendrite and spine were decreased by Aβ 42 oligomers, which can be prevented by rosiglitazone. In conclusion, our data suggested that rosiglitazone prevents Aβ 42 oligomers-induced impairment via increasing mitochondrial numbers in the dendrite and spine, improving synapse formation and plasticity. This process is most likely through the PPARγ-dependent pathway and in concentration and time dependent manners. The study provides novel insights into the mechanisms for the protective effects of rosiglitzone on AD. © 2014 - IOS Press and the authors. All rights reserved.

Publication Date

1-1-2014

Publication Title

Journal of Alzheimer's Disease

ISSN

13872877

Volume

39

Issue

2

First Page

239

Last Page

251

Digital Object Identifier (DOI)

10.3233/JAD-130680

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