BDNF mRNA splice variants display activity-dependent targeting to distinct hippocampal laminae

BDNF mRNA splice variants display activity-dependent targeting to distinct hippocampal laminae
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DOI:
10.1016/j.mcn.2007.08.011
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发表时间:
2008-01-01
影响因子:
3.5
通讯作者:
Tongiorgi, E.
Tongiorgi, E.
中科院分区:
医学3区
文献类型:
--
作者:
Chiaruttini, C.;Sonego, M.;Tongiorgi, E.

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脑源性神经营养因子(BDNF)可能根据其不同的亚细胞作用位点(体细胞、树突、轴突)发挥不同的作用。这些不同的作用可以解释相互矛盾的发现,例如,BDNF可能有利于或反对癫痫发生。在刺激大鼠海马主要神经元的树突中积累BDNF mRNA后,我们确定了5种BDNF剪接变异体在树突中的分布(癫痫性发作)。在基础条件下,树突中未检测到BDNF mRNA剪接变异,而在对癫痫性发作的反应中,树突中发现了特异性剪接变异。给药3小时后,在树突中发现外显子VI和外显子II剪接变异体,而外显子I和IV转录本显示出严格的体细胞定位。给药3小时后,树突中仅发现外显子VI。这些数据表明,不同剪接变异体的调控表达可能提供了一种空间编码,以确保BDNF递送到细胞体细胞或沿树突的精确目的地。(C) 2007爱思唯尔公司版权所有。
Brain-derived neurotrophic factor (BDNF) may exert contrasting effects depending on its different subcellular sites of action (soma, dendrites, axons). These contrasting effects may explain contradictory findings, for example that BDNF may favour or oppose epileptogenesis. We determined the distribution of five BDNF splice variants in the soma and dendrites of rat hippocampal principal neurons, after application of stimuli that prompt BDNF mRNA accumulation in dendrites (epileptogenic seizures). Under basal conditions, no BDNF mRNA splice variant was detectable in dendrites, while specific splice variants were found in dendrites in response to epileptogenic seizures. Three hours after pilocarpine administration, exon VI and exon II splice variants were found in dendrites, while exons I and IV transcripts displayed a strictly somatic localization. Three hours after kainate administration, only exon VI was found in dendrites. These data suggest that the regulated expression of different splice variants may provide a spatial code to ensure the delivery of BDNF to precise destinations in the cell soma or along the dendrites. (C) 2007 Elsevier Inc. All rights reserved.