期刊
NEUROBIOLOGY OF AGING
卷 34, 期 2, 页码 551-561出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2012.04.018
关键词
Alzheimer's disease; Amyloid beta; Dendritic spines; Postsynaptic density-95 protein; Synapses; Tauroursodeoxycholic acid
资金
- Fundacao para a Ciencia e Tecnologia (FCT), Lisbon, Portugal [PTDC/SAU-NMC/112636/2009, PTDC/SAU-NMC/117877/2010, Pest-OE/SAU/UI4013/2011]
- FCT [SFRH/BPD/40623/2007, SFRH/BPD/34603/2007, SFRH/BPD/47376/2008, SFRH/BD/27761/2006]
- Fundação para a Ciência e a Tecnologia [SFRH/BPD/47376/2008, SFRH/BPD/40623/2007, SFRH/BPD/34603/2007, PTDC/SAU-NMC/112636/2009, SFRH/BD/27761/2006] Funding Source: FCT
Synapses are considered the earliest site of Alzheimer's disease (AD) pathology, where synapse density is reduced, and synaptic loss is highly correlated with cognitive impairment. Tauroursodeoxycholic acid (TUDCA) has been shown to be neuroprotective in several models of AD, including neuronal exposure to amyloid beta (A beta) and amyloid precursor protein (APP)/presenilin 1 (PS1) double-transgenic mice. Here, we show that TUDCA modulates synaptic deficits induced by A beta in vitro. Specifically, TUDCA reduced the downregulation of the postsynaptic marker postsynaptic density-95 (PSD-95) and the decrease in spontaneous miniature excitatory postsynaptic currents (mEPSCs) frequency, while increasing the number of dendritic spines. This contributed to the induction of more robust and synaptically efficient neurons, reflected in inhibition of neuronal death. In vivo, TUDCA treatment of APP/PS1 mice abrogated the decrease in PSD-95 reactivity in the hippocampus. Taken together, these results expand the neuroprotective role of TUDCA to a synaptic level, further supporting the use of this molecule as a potential therapeutic strategy for the prevention and treatment of AD. (C) 2013 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据