慢性和急性抗抑郁治疗后脑源性神经营养因子(BDNF)mRNA亚型的表达分析

Expression analysis of brain-derived neurotrophic factor (BDNF) mRNA isoforms after chronic and acute antidepressant treatment.

作者信息

Altieri Mario, Marini Francesca, Arban Roberto, Vitulli Giovanni, Jansson Birger O

机构信息

Centre of Excellence for Drug Discovery, Psychiatry, GlaxoSmithKline Research Centre, via Fleming 4, I-37135 Verona, Italy.

出版信息

Brain Res. 2004 Mar 12;1000(1-2):148-55. doi: 10.1016/j.brainres.2003.12.028.

Abstract

The neurotrophin brain-derived neurotrophic factor (BDNF) is considered to be a key factor for neuronal survival, differentiation and plasticity. According to a proposed hypothetical model BDNF expression might play a central role in the pathogenesis of depression. The BDNF gene is rather complex in its structure and it can express four different mRNA isoforms by alternative splicing, each producing the same protein. This might reflect fine tuning of gene regulation by different signalling networks. Since the BDNF gene has been reported to be upregulated by antidepressants, the expression of the four BDNF mRNA isoforms was measured by real-time quantitative RT-PCR in rat hippocampi after chronic and acute treatment with the antidepressant drug fluoxetine and GR205171, a selective NK-1 receptor antagonist with anxiolytic-like properties. The aim of this study was to test the hypothesis of differential regulation of the mRNA isoforms by those compounds. Our results indicate that the expression of BDNF mRNA isoforms is not affected by chronic or acute treatment with fluoxetine or GR205171.

摘要

神经营养因子脑源性神经营养因子(BDNF)被认为是神经元存活、分化和可塑性的关键因素。根据一个提出的假说模型,BDNF表达可能在抑郁症的发病机制中起核心作用。BDNF基因结构相当复杂,它可通过可变剪接表达四种不同的mRNA亚型,每种亚型产生相同的蛋白质。这可能反映了不同信号网络对基因调控的精细调节。由于据报道BDNF基因可被抗抑郁药上调,因此在用抗抑郁药氟西汀和GR205171(一种具有抗焦虑样特性的选择性NK-1受体拮抗剂)进行慢性和急性治疗后,通过实时定量RT-PCR测定大鼠海马中四种BDNF mRNA亚型的表达。本研究的目的是检验这些化合物对mRNA亚型进行差异调节的假说。我们的数据表明,BDNF mRNA亚型的表达不受氟西汀或GR205171慢性或急性治疗的影响。

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