Gene Expression after Cochlear Removal in Cochlear Nucleus at P7 and P21

Deprivation of peripheral nerve input by cochlear removal in young mice results in dramatic neuron death in the cochlear nucleus (CN). The same manipulation in older mice does not result in significant loss. The molecular basis of this critical period of vulnerability remains largely unknown. Here we identified genes regulated at early time points after cochlear removal at ages when neurons are vulnerable (postnatal day (P)7) or invulnerable (P21) to this challenge. Afferent deprivation regulated very different sets of genes at P7 and P21. These genes showed a variety of functions at both ages, but surprisingly there was no net increase in pro-apoptotic genes at P7. A large set of upregulated immune-related genes was identified at P21. Keywords: Time Course after Cochlear Removal, Age Comparison Mice received unilateral cochlear removals. At 6, 12, 24, and 48 hours after surgery, the CN ipsilateral and contralateral were removed, and RNA isolated from separate pools of tissue for each replicate. Deafferented CN were compared to age-matched and time-matched contralateral, control CN to identify genes regulated by cochlear removal at age P7 and P21.

幼年小鼠经耳蜗切除剥夺外周神经传入信号后，其耳蜗核（cochlear nucleus, CN）会出现显著的神经元死亡。对老年小鼠实施相同操作，则不会引发显著的神经元丢失。这种易损性关键时期的分子机制目前仍未完全明确。
本研究选取神经元对该干预存在易损性的年龄（出生后第7天，postnatal day 7, P7）与不存在易损性的年龄（P21），鉴定了耳蜗切除后早期时间点的差异调控基因。传入信号剥夺在P7与P21两个年龄点所调控的基因集存在显著差异。两个年龄组的差异基因均涉及多种生物学功能，但令人意外的是，P7组的促凋亡基因并未出现净上调。而在P21组中，我们鉴定到大量上调的免疫相关基因。
关键词：耳蜗切除后的时间进程、年龄对比
实验小鼠接受单侧耳蜗切除手术。分别于术后6、12、24及48小时采集双侧耳蜗核（同侧与对侧）组织，每份重复样本均取自独立的组织混合池，并从中提取RNA。将去传入的耳蜗核与同年龄、同时间点的对侧对照耳蜗核进行比对，以鉴定P7与P21年龄组中由耳蜗切除所调控的差异表达基因。