Attenuated BDNF-induced upregulation of GABAergic markers in neurons lacking Xbp1
Attenuated BDNF-induced upregulation of GABAergic markers in neurons lacking Xbp1
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DOI：
10.1016/j.bbrc.2008.09.059
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发表时间：
2008-11-28
影响因子：
3.1
通讯作者：
Kato, Tadafumi
中科院分区：
文献类型：
--
作者：
Hayashi, Akiko;Kasahara, Takaoki;Kato, Tadafumi
XBP 1是一种由非常规剪接诱导的转录因子，与内质网、应激有关，在发育中起作用。脑源性神经营养因子（BDNF）导致Xbp 1 mRNA在神经突中的剪接，而Xbp 1是BDNF诱导的神经突延伸和分支所必需的。为了寻找Xbp 1如何在神经发育中发挥作用的分子机制，在胚胎第12.5天从Xbp 1敲除小鼠获得的初级端脑神经元中进行全面的基因表达分析。通过在野生型神经元中寻找BDNF诱导的基因，但在Xbp 1敲除小鼠中没有，我们发现三种GABA能标记物，生长抑素（Sst），神经肽Y（Npy）和钙结合蛋白（Calb 1）的上调在Xbp 1敲除神经元中受到损害。定量RT-PCR证实Xbp 1基因敲除神经元中Npy和Calb 1的上调减弱。这一发现可能与Xbp 1基因敲除神经元中BDNF诱导的轴突延伸受损有关。(C)2008年爱思唯尔公司All rights reserved.
XBP1 is a transcription factor induced by unconventional splicing associated with endoplasmic reticulum, stress and plays a role in development. Brain-derived neurotrophic factor (BDNF) causes splicing of Xbp1 mRNA in neurites, and Xbp1 is required for BDNF-induced neurite extension and branching. To search for the molecular mechanisms of how Xbp1 Plays a role in neural development, comprehensive gene expression analysis was performed in primary telencephalic neurons obtained from Xbp1 knockout mice at embryonic day 12.5. By searching for the genes induced by BDNF in wild type neurons but not in Xbp1 knockout mice, we found that upregulation of three GABAergic markers, somatostatin (Sst), neuropeptide Y (Npy), and calbindin (Calb1), were compromised in Xbp1 knockout neurons. Attenuated upregulation of Npy and Calb1 in Xbp1 knockout neurons was confirmed by quantitative RT-PCR. This finding may be relevant to impaired BDNF-induced neurite extension in Xbp1 knockout neurons. (C) 2008 Elsevier Inc. All rights reserved.