Altered expression of genes regulating inflammation and synaptogenesis during regrowth of afferent neurons to cochlear hair cells.
Altered expression of genes regulating inflammation and synaptogenesis during regrowth of afferent neurons to cochlear hair cells.
复制标题
DOI：
10.1371/journal.pone.0238578
复制
发表时间：
2020
期刊：
影响因子：
3.7
通讯作者：
Stankovic KM
中科院分区：
文献类型：
--
作者：
Wu CC;Brugeaud A;Seist R;Lin HC;Yeh WH;Petrillo M;Coppola G;Edge ASB;Stankovic KM
螺旋神经节神经元构成听觉毛细胞和大脑之间的主要联系。成年哺乳动物耳损伤后，螺旋神经节传入纤维及其与毛细胞的突触没有明显的再生。我们研究了新生儿耳蜗外植模型中红藻氨酸诱导的突触破坏后基因表达的变化，在该模型中外周纤维和传入突触确实再生。我们比较了损伤后早期、纤维和突触再生过程中以及体外再生完成后的基因表达。这些分析揭示了基于p<0.005的阈值的总共2.5%的差异调节转录物（24，000个中的588个）。炎症反应基因以及参与神经回路再生的基因在毛细胞所在的螺旋神经节神经元和Corti器官中上调。在几个时间点上调的突出基因包括在神经发生（Elavl4和Sox 21）、神经生长（Ntrk3和Ppplrlc）、轴突引导（Rgmb和Sema7a）、突触发生（Nlgn 2和Psd 2）和突触囊泡功能（Syt 8和Syn 1）中起作用的基因。免疫组织化学和原位杂交分析的基因，以前没有被描述在耳蜗证实了他们的耳蜗表达。这些基因的表达的时间过程表明，红藻氨酸治疗导致螺旋神经节神经元的两个阶段的反应：急性反应与炎症一致，随后是神经再生基因的上调。这些纤维再生过程中激活的基因的鉴定表明，候选人可以有针对性地增强成人耳朵的再生。
The spiral ganglion neurons constitute the primary connection between auditory hair cells and the brain. The spiral ganglion afferent fibers and their synapse with hair cells do not regenerate to any significant degree in adult mammalian ears after damage. We have investigated gene expression changes after kainate-induced disruption of the synapses in a neonatal cochlear explant model in which peripheral fibers and the afferent synapse do regenerate. We compared gene expression early after damage, during regeneration of the fibers and synapses, and after completion of in vitro regeneration. These analyses revealed a total of 2.5% differentially regulated transcripts (588 out of 24,000) based on a threshold of p<0.005. Inflammatory response genes as well as genes involved in regeneration of neural circuits were upregulated in the spiral ganglion neurons and organ of Corti, where the hair cells reside. Prominent genes upregulated at several time points included genes with roles in neurogenesis (Elavl4 and Sox21), neural outgrowth (Ntrk3 and Ppp1r1c), axonal guidance (Rgmb and Sema7a), synaptogenesis (Nlgn2 and Psd2), and synaptic vesicular function (Syt8 and Syn1). Immunohistochemical and in situ hybridization analysis of genes that had not previously been described in the cochlea confirmed their cochlear expression. The time course of expression of these genes suggests that kainate treatment resulted in a two-phase response in spiral ganglion neurons: an acute response consistent with inflammation, followed by an upregulation of neural regeneration genes. Identification of the genes activated during regeneration of these fibers suggests candidates that could be targeted to enhance regeneration in adult ears.
登录
查看更多内容
影响因子：
3.7
作者：
Juknat A;Pietr M;Kozela E;Rimmerman N;Levy R;Gao F;Coppola G;Geschwind D;Vogel Z
通讯作者：
Vogel Z
影响因子：
3
作者：
Brugeaud, Aurore;Tong, Mingjie;Edge, Albert S. B.
通讯作者：
Edge, Albert S. B.
影响因子：
5.3
作者：
Kujawa, SG;Liberman, MC
通讯作者：
Liberman, MC
影响因子：
6.2
作者：
Boesmans, Werend;Hao, Marlene M.;Vanden Berghe, Pieter
通讯作者：
Vanden Berghe, Pieter
影响因子：
5.3
作者：
Eva, Richard;Crisp, Sarah;Fawcett, James W.
通讯作者：
Fawcett, James W.