Rapid induction of BDNF expression in the hippocampus during immobilization stress challenge in adult rats

Rapid induction of BDNF expression in the hippocampus during immobilization stress challenge in adult rats
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DOI:
10.1002/hipo.10109
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发表时间:
2003-01-01
期刊:
影响因子:
3.5
通讯作者:
Tapia-Arancibia, L
Tapia-Arancibia, L
中科院分区:
医学3区
文献类型:
--
作者:
Marmigère, F;Givalois, L;Tapia-Arancibia, L

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脑源性神经营养因子(BDNF)在海马体中强烈表达,在那里它与记忆过程有关。在中枢神经系统中,一些学习过程,以及脑损伤,包括压力,诱导BDNF mRNA表达的修改。由于应激和记忆似乎共享一些神经元通路,我们研究了短时间的固定应激反应中BDNF mRNA和BDNF肽的变化。使用核糖核酸酶保护试验,我们表明,短时间的压力应用程序诱导的BDNF mRNA水平在整个大鼠海马的显着增加(在60分钟)。BDNF mRNA含量的变化似乎反映了含有外显子1、11和111的BDNF转录本的表达增加,这些外显子在此时也被显著修饰。应激诱导的BDNF转录水平变化的时间过程显示,含有外显子III的mRNA是第一个增加,显着升高15分钟,在60分钟达到最高水平,作为BDNF转录含有外显子I和II。然而,在较长的时间的压力(180分钟),BDNF mRNA水平下降,以及含有外显子IV的mRNA。离散海马层的原位杂交分析表明,BDNF mRNA的表达增加早在15分钟在大多数海马区域,标记细胞的数量没有修改。在60分钟时测定了相同的信号模式,尽管不太明显,但此时在CA 3层中观察到BDNF阳性细胞的显著增加。肽,通过免疫测定,显着增加后180分钟的应激暴露,而在300分钟,水平与对照动物中测量的那些相似。这些数据表明,BDNF表达的快速变化可能是维持海马稳态的代偿反应的一部分,也可能是科普新刺激的神经元可塑性的一种形式。(C)2003 Wiley-Liss,Inc.
Brain-derived neurotrophic factor (BDNF) is strongly expressed in the hippocampus, where it has been associated with memory processes. In the central nervous system, some learning processes, as well as brain insults, including stress, induce modifications in BDNF mRNA expression. Because stress and memory appear to share some neuronal pathways, we studied BDNF mRNA and BDNF peptide variations in response to short times of immobilization stress. Using an RNase protection assay, we demonstrated that short-time stress application induced a significant increase (at 60 min) in BDNF mRNA levels in the whole rat hippocampus. Changes in BDNF mRNA content appear to reflect increased expression of BDNF transcripts containing exons 1, 11, and 111, that were also significantly modified at this time. The time course of stress-induced changes in BDNF transcript levels revealed that mRNA containing exon III was the first increased, significantly elevated by 15 min, attaining maximal levels at 60 min, as BDNF transcripts containing exons I and II. However, at longer times of stress (180 min), BDNF mRNA levels were decreased as well as mRNA containing exon IV. In situ hybridization analysis of discrete hippocampal layers demonstrated that BDNF mRNA expression increased as early as 15 min in most hippocampal regions, with no modification in the number of labeled cells. The same signal pattern, although less pronounced, was determined at 60 min, but at this time a significant increase in BDNF-positive cells was visualized in the CA3 layer. The peptide, measured by immunoassay, was significantly augmented after 180 min of stress exposure whereas at 300 min, levels were similar to those measured in control animals. These data suggest that rapid changes in BDNF expression may be part of a compensatory response to preserve hippocampal homeostasis or a form of neuronal plasticity to cope with new stimuli. (C) 2003 Wiley-Liss, Inc.