Afferent deprivation elicits a transcriptional response associated with neuronal survival after a critical period in the mouse cochlear nucleus.
Afferent deprivation elicits a transcriptional response associated with neuronal survival after a critical period in the mouse cochlear nucleus.
复制标题
传入剥夺引起了小鼠耳蜗核中关键时期后与神经元存活相关的转录反应。
DOI：
10.1523/jneurosci.2697-08.2008
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发表时间：
2008-10-22
影响因子：
5.3
通讯作者：
Rubel, Edwin W.
中科院分区：
文献类型：
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作者：
Harris, Julie A.;Iguchi, Fukuichiro;Seidl, Armin H.;Lurie, Diana I.;Rubel, Edwin W.
在发育中的感觉系统中，突触连接的可塑性增强和对传入活动操纵的敏感性增强的机制还没有很好地理解。一个例子是在移除对年轻哺乳动物和鸟类的耳蜗核（CN）的传入输入后发生的快速和戏剧性的神经元死亡。这个关键时期的神经元脆弱性和过渡到独立的传入输入的生存的分子基础仍有待确定。在这里，我们使用微阵列分析，真实的时间RT PCR，和免疫组化的小鼠CN显示，去传入神经的结果在脆弱（出生后第7天（P））和无懈可击（P21）CN的调节基因的显着不同的设置。一个意想不到的大集合的免疫相关基因诱导传入剥夺后的关键时期，这对应于在同一时间范围内的神经胶质细胞增殖。凋亡基因的表达并没有高度调节后传入剥夺的脆弱CN，但令人惊讶的是，增加后，在P21，当所有的神经元最终生存。第8神经的药理活性阻断模仿传入剥夺的传入剥夺调节基因的一个子集，表明存在一个额外的因素，不依赖于动作电位介导的信号传导，也是负责转录的变化。总体而言，我们的研究结果表明，在这一关键时期的细胞死亡机制主要是组成，而在关键时期后，神经元的生存可以积极促进组成和诱导基因表达。
The mechanisms underlying enhanced plasticity of synaptic connections and susceptibilities to manipulations of afferent activity in developing sensory systems are not well understood. One example is the rapid and dramatic neuron death that occurs after removal of afferent input to the cochlear nucleus (CN) of young mammals and birds. The molecular basis of this critical period of neuronal vulnerability and the transition to survival independent of afferent input remains to be defined. Here we used microarray analyses, real time RT PCR, and immunohistochemistry of the mouse CN to show that deafferentation results in strikingly different sets of regulated genes in vulnerable (postnatal day (P) 7) and invulnerable (P21) CN. An unexpectedly large set of immune-related genes was induced by afferent deprivation after the critical period, which corresponded with glial proliferation over the same time frame. Apoptotic gene expression was not highly regulated in the vulnerable CN after afferent deprivation but, surprisingly, did increase after deafferentation at P21, when all neurons ultimately survive. Pharmacological activity blockade in the 8th nerve mimicked afferent deprivation for only a subset of the afferent deprivation regulated genes, indicating the presence of an additional factor not dependent on action potential-mediated signaling that is also responsible for transcriptional changes. Overall, our results suggest that the cell death machinery during this critical period is mainly constitutive, whereas after the critical period neuronal survival could be actively promoted by both constitutive and induced gene expression.