Dual response of BDNF to sublethal concentrations of β-amyloid peptides in cultured cortical neurons

Dual response of BDNF to sublethal concentrations of β-amyloid peptides in cultured cortical neurons
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DOI:
10.1016/j.nbd.2009.10.004
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发表时间:
2010-01-01
影响因子:
6.1
通讯作者:
Tapia-Arancibia, L.
Tapia-Arancibia, L.
中科院分区:
医学1区
文献类型:
--
作者:
Aliaga, E.;Silhol, M.;Tapia-Arancibia, L.

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β-淀粉样蛋白(Aβ)沉积是阿尔茨海默病(AD)的一个重要病理标志。然而。低水平的 Aβ 可能会在神经变性发生之前改变关键的内源性保护系统。我们检查了亚致死浓度的 Aβ 对总 BDNF (panBDNF)、BDNF 转录本(I、II、IV 和 VI)的时间过程影响。 trkB.FL。培养的皮质神经元中的 trkB.T1 和 p75(NGFR) mRNA 表达 我们已经表明,Aβ 对 BDNF mRNA 表现出双重反应,即短时间(3-5 小时)增加和长时间(24 或 48 小时)急剧减少。 BDNF 表达的早期增加似乎是由转录物 I 和 IV 的表达增加驱动的。 BDNF 下降是特异性的,因为检查的其他 mRNA 没有发生这种情况。 BDNF 蛋白含量显示出相似的特征,但并没有像其编码 mRNA 那样急剧减少。这些观察结果可能有助于解释 AD 初始阶段观察到的认知缺陷。 (C) 2009 Elsevier Inc. 保留所有权利。
Beta-amyloid (A beta) deposition is one important pathological hallmark in Alzheimer's disease (AD). However. low levels of A beta may modify critical endogenous protection systems before neurodegeneration occurs. We examined the time-course effect of sublethal concentrations of A beta on total BDNF (panBDNF), BDNF transcripts (I, II, IV and VI). trkB.FL. trkB.T1 and p75(NGFR) mRNA expression in cultured cortical neurons We have shown that A beta exhibited a dual response on BDNF mRNA, i.e an increase at short times (3-5 h) and a dramatic decrease at longer times (24 or 48 h). The early increase in BDNF expression seems to be driven by increased expression of transcripts I and IV. The BDNF drop was specific since did not occur for other mRNAs examined. The BDNF protein content showed a similar profile but did not follow the dramatic reduction as its encoding mRNA. These observations may help to explain cognitive deficits observed at initial stages of AD. (C) 2009 Elsevier Inc. All rights reserved.