Effects of lithium and deafferentation on expression of glycogen synthase kinase-3β, NFκB, β-catenin and pCreb in the chick cochlear nucleus
Effects of lithium and deafferentation on expression of glycogen synthase kinase-3β, NFκB, β-catenin and pCreb in the chick cochlear nucleus
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DOI：
10.1016/j.brainres.2008.01.076
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发表时间：
2008-04-08
期刊：
影响因子：
2.9
通讯作者：
Hyson, Richard L.
中科院分区：
文献类型：
--
作者：
Bush, Angela L.;Hyson, Richard L.
鸟类脑干作为一个有用的模型来回答传入活动如何影响靶神经元的生存能力的问题。鸟类耳蜗核、大细胞核（NM）中大约20-30%的神经元在传入神经阻滞后死亡（即，耳蜗切除引起的耳聋）。有趣的是，Bcl-2 mRNA（而不是蛋白质）在20-30%的NM神经元后，传入神经阻滞上调。我们最近发现，锂的慢性治疗上调神经保护蛋白Bcl-2，并增加神经元的存活率以下deafferentation。这两种操作后导致Bcl-2表达上调的途径尚不清楚。本实验检测了锂给药后和传入神经阻滞后糖原合成酶激酶-3 β（Gsk-3 β）和转录因子核因子κ B（NF κ B）、β-连环蛋白和pCreB的变化。已知这些分子受到锂的影响，并在其他模型系统中调节Bcl-2的表达。锂降低免疫标记的GSK-3 β和增加表达的所有三个转录因子。然而，去传入并不改变GSK-3 β或NF κ B，导致β-连环蛋白表达降低，但确实增加了pCreB免疫活性。虽然这是可能的，pCreb是一个共同的链接在Bcl-2的调节后，这两个操纵，pCreb标记的时间和分布表明，它不是唯一的决定因素Bcl-2上调后去传入。锂和去传入神经对Bcl-2基因表达的调节可能涉及不同的分子途径。(c)2008 Elsevier B. V.保留所有权利。
The avian brainstem serves as a useful model to answer the question of how afferent activity influences the viability of target neurons. Approximately 20-30% of neurons in the avian cochlear nucleus, nucleus magnocellularis (NM) die following deafferentation (i.e., deafness produced by cochlea removal). Interestingly, Bcl-2 mRNA (but not protein) is upregulated in 20-30% of NM neurons following deafferentation. We have recently shown that chronic treatments of lithium upregulates the neuroprotective protein Bcl-2 and increases neuronal survival following deafferentation. The pathways leading to the upregulation of Bcl-2 expression following these two manipulations are unknown. The present experiments examine changes in glycogen synthase kinase-3 beta (Gsk-3 beta), and transcription factors nuclear factor kappa B (NF kappa B), beta-catenin, and pCreb following lithium administration and following deafferentation. These molecules are known to be influenced by lithium and to regulate Bcl-2 expression in other model systems. Lithium decreased immunolabeling for Gsk-3 beta and increased expression for all three transcription factors. Deafferentation, however, did not alter Gsk-3 beta or NF kappa B, resulted in lower beta-catenin expression, but did increase pCreb immunore activity. While it is possible that pCreb is a common link in the regulation of Bcl-2 following these two manipulations, the timing and distribution of pCreb labeling suggests that it is not the sole determinant of Bcl-2 upregulation following deafferentation. It is likely that the regulation of Bcl-2 gene expression by lithium and by deafferentation involves different molecular pathways. (c) 2008 Elsevier B.V. All rights reserved.