Anterograde trafficking of neurotrophin-3 in the adult olfactory system in vivo.

Anterograde trafficking of neurotrophin-3 in the adult olfactory system in vivo.
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DOI:
10.1016/j.expneurol.2012.12.010
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发表时间:
2013-03
影响因子:
5.3
通讯作者:
Guthrie KM
Guthrie KM
中科院分区:
医学2区
文献类型:
--
作者:
Liu H;Lu M;Guthrie KM

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嗅觉系统在一生中不断地将新的神经元整合到功能回路中。来自鼻腔嗅觉感觉神经元(OSN)的轴突与主嗅球的二尖瓣细胞、簇状细胞和小叶周围细胞(PG)突触,在正常生理条件下,OSN群体内部的低水平更新导致新的轴突长入。成体前脑室下区球间神经元亚群不断被细胞凋亡所消除,并被来源于前脑室下区祖细胞的新神经元所取代。新神经元的整合,包括与感觉轴突接触的PG细胞,导致成人嗅球回路的持续重组。调节这种适应性结构可塑性的机制尚不清楚,但这一过程让人想起早期神经系统的发育。在发育过程中,神经营养因子在控制神经元存活和连通性方面的作用已经得到证实,这导致人们猜测,在成人中,osn与其目标球神经元之间的营养相互作用可能介导了一些相同的过程。许多不同的营养因子及其同源受体在成人嗅觉通路中表达。神经营养因子-3 (NT3)就是其中之一,在NT3启动子下表达lacZ的转基因报告小鼠中β -半乳糖苷酶的表达反映了这一点。利用免疫细胞化学、激光捕获RNA的实时PCR和腺病毒介导的NT3融合肽的体内基因转移等多种方法,我们证明了osn表达NT3并顺行转运到嗅球。我们还观察到,在用带有血凝素(HA)标记的编码NT3的腺病毒处理的小鼠中,一部分表达TrkC神经营养因子受体的球泡神经元对HA具有免疫反应性,这表明它们从受感染的感觉神经元获得融合肽。因此,我们的研究结果提供了证据,表明osn可能是成年小鼠嗅球营养信号的传入来源。
The olfactory system continuously incorporates new neurons into functional circuits throughout life. Axons from olfactory sensory neurons (OSNs) in the nasal cavity synapse on mitral, tufted and periglomerular (PG) cells in the main olfactory bulb, and low levels of turnover within the OSN population results in ingrowth of new axons under normal physiological conditions. Subpopulations of bulb interneurons are continually eliminated by apoptosis, and are replaced by new neurons derived from progenitors in the adult forebrain subventricular zone. Integration of new neurons, including PG cells that are contacted by sensory axons, leads to ongoing reorganization of adult olfactory bulb circuits. The mechanisms regulating this adaptive structural plasticity are not all known, but the process is reminiscent of early nervous system development. Neurotrophic factors have well-established roles in controlling neuronal survival and connectivity during development, leading to speculation that trophic interactions between OSNs and their target bulb neurons may mediate some of these same processes in adults. A number of different trophic factors and their cognate receptors are expressed in the adult olfactory pathway. Neurotrophin-3 (NT3) is among these, as reflected by beta-galactosidase expression in transgenic reporter mice expressing lacZ under the NT3 promoter. Using a combination of approaches, including immunocytochemistry, real-time PCR of laser-captured RNA, and adenovirus-mediated gene transfer of NT3 fusion peptides in vivo, we demonstrate that OSNs express and anterogradely transport NT3 to the olfactory bulb. We additionally observe that in mice treated with adenovirus encoding NT3 tagged with hemagglutinin (HA), a subset of bulb neurons expressing the TrkC neurotrophin receptor are immunoreactive for HA, suggesting their acquisition of the fusion peptide from infected sensory neurons. Our results therefore provide evidence that OSNs may serve as an afferent source of trophic signals for the adult mouse olfactory bulb.
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发表时间: 1997-01-01
影响因子: 5.3
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