Protective effect of BDNF against beta-amyloid induced neurotoxicity in vitro and in vivo in rats

Protective effect of BDNF against beta-amyloid induced neurotoxicity in vitro and in vivo in rats
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DOI:
10.1016/j.nbd.2008.05.012
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发表时间:
2008-09-01
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:
Arancibia, S.;Silhol, M.;Tapia-Arancibia, L.

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我们在大鼠体内和体外研究了 BDNF 对 F-淀粉样蛋白诱导的神经毒性的潜在保护作用。在神经元培养中,BDNF 对 A beta(1-42) 和 A beta(25-35) 诱导的神经元毒性具有特异性和剂量反应保护作用。它完全逆转了Aβ(1-42)引起的毒性作用和部分逆转了Aβ(25-35)引起的毒性作用。这些效应涉及 TrkB 受体激活,因为它们被 K252a 抑制。催化 BDNF 受体 (TrkB.FL) 在体外定位于皮质神经元(mRNA 和蛋白质)。在体内实验中,将 A beta(25-35) 注射到灰套或第三脑室,7 天后测量几个参数以评估潜在的 A beta(25-35)/BDNF 相互作用,即局部测量 BDNF 释放、表达 SRIH mRNA 的海马门细胞数量和评估胼胝体损伤(形态学检查、固缩核计数和轴突标记)抗 MBP 抗体)。我们得出的结论是 BDNF 具有针对 Aβ 肽毒性作用的神经保护特性。 (C) 2008 年,爱思唯尔公司出版。
We examined the potential protective effect of BDNF against F-amyloid-induced neurotoxicity in vitro and in vivo in rats. In neuronal cultures, BDNF had specific and dose-response protective effects on neuronal toxicity induced by A beta(1-42) and A beta(25-35). It completely reversed the toxic action induced by A beta(1-42) and partially that induced by A beta(25-35). These effects involved TrkB receptor activation since they were inhibited by K252a. Catalytic BDNF receptors (TrkB.FL) were localized in vitro in cortical neurons (mRNA and protein). In in vivo experiments, A beta(25-35) was administered into the indusium griseum or the third ventricle and several parameters were measured 7 days later to evaluate potential A beta(25-35)/BDNF interactions, i.e. local measurement of BDNF release, number of hippocampal hilar cells expressing SRIH mRNA and assessment of the corpus callosum damage (morphological examination, pyknotic nuclei counting and axon labeling with anti-MBP antibody). We conclude that BDNF possesses neuroprotective properties against toxic effects of A beta peptides. (C) 2008 Published by Elsevier Inc.