Agonists of peroxisome proliferator-activated receptor-γ attenuate the Aβ-mediated impairment of LTP in the hippocampus in vitro
Agonists of peroxisome proliferator-activated receptor-γ attenuate the Aβ-mediated impairment of LTP in the hippocampus in vitro
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DOI：
10.1016/j.neuropharm.2005.03.009
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发表时间：
2005-09-01
影响因子：
4.7
通讯作者：
Herron, CE
中科院分区：
文献类型：
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作者：
Costello, DA;O'Leary, DM;Herron, CE
我们在此提供的数据表明，过氧化物酶体增殖物激活受体-γ (PPAR gamma) 的激动剂可以减弱 β-淀粉样肽 (A beta) 的作用。阿尔茨海默病与 A β 水平升高和 PPAR γ 表达增强有关。在本研究中，我们确定应用 A beta([1-40]) 可能会在体外损害海马强直后增强 (PTP) 和长时程增强 (LTP)。我们研究了 PPAR γ 激动剂的作用；曲格列酮、环格列酮和 15-脱氧-Delta(12,14) 前列腺素 J(2) (PGJ(2)) 对 CA1 区突触传递和可塑性的影响。环格列酮和 PGJ2 均显着增加基线突触传递，而不改变配对脉冲促进。 PGJ(2) 显着降低 LTP，而环格列酮和曲格列酮没有显着效果。此外，每种配体的预先应用减轻了先前观察到的 A beta([1-40]) 介导的 LTP 损伤。曲格列酮对 A beta([1-40]) 介导的 UP 损伤的作用不能被 PPAR γ 拮抗剂 GW-9662 逆转。这些发现表明，PPAR γ 激动剂减弱了 A 对 LTP 的影响，并支持这些药物可能用于缓解阿尔茨海默病的症状。我们还认为 PPAR γ 激动剂可能在体外调节海马 LTP 的表达。 (c) 2005 Elsevier Ltd. 保留所有权利。
The data we present here suggest that agonists of peroxisome proliferator-activated receptor-gamma (PPAR gamma) can attenuate the effects of beta-amyloid peptide (A beta). Alzheimer's disease is associated with elevated levels of A beta, and enhanced expression of PPAR gamma. In this study, we determined that application of A beta([1-40]) could impair hippocampal post-tetanic potentiation (PTP) and long-term potentiation (LTP) in vitro. We investigated the effects of PPAR gamma agonists; troglitazone, ciglitazone and 15-deoxy-Delta(12,14) prostaglandin J(2) (PGJ(2)) on synaptic transmission and plasticity in area CA1. Both ciglitazone and PGJ2 increased baseline synaptic transmission significantly, without altering paired-pulse facilitation. PGJ(2) produced a significant reduction in LTP, whereas ciglitazone and troglitazone had no significant effect. In addition, prior application of each ligand attenuated the previously observed A beta([1-40])-mediated impairment of LTP. The effect of troglitazone on the A beta([1-40])-mediated impairment of UP was not reversed by the PPAR gamma antagonist, GW-9662. These findings demonstrate that PPAR gamma agonists attenuate the effects of A on LTP, and support the potential use of these agents to alleviate the symptoms of Alzheimer's disease. We also suggest that PPAR gamma agonists may regulate expression of hippocampal LTP in vitro. (c) 2005 Elsevier Ltd. All rights reserved.