P75 nerve growth factor receptors modulate development of GnRH neurons and olfactory ensheating cells.

P75 nerve growth factor receptors modulate development of GnRH neurons and olfactory ensheating cells.
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DOI:
10.3389/fnins.2013.00262
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发表时间:
2013
影响因子:
4.3
通讯作者:
Wray S
Wray S
中科院分区:
医学2区
文献类型:
--
作者:
Raucci F;Tiong JD;Wray S

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神经生长因子受体(p75 NGFR)在发育中的嗅觉系统和促性腺激素释放激素-1(GnRH)系统的时空定位的特点和其作用分析使用p75 NGFR基因敲除小鼠和鼻外植体。在出生前,p75 NGFR表达于GnRH神经元和嗅鞘细胞(OECs)。在p75 NGFR敲除小鼠中,与野生型相比,未检测到GnRH细胞数量的变化。然而,在null小鼠中,发现GnRH神经元的分布发生了变化,一小群GnRH细胞向正中隆起进一步向尾侧迁移。此外,GAD 67阳性嗅轴突和GFAP阳性OEC纤维均减少。急性给药的p75 NGFR阻断剂GnRH细胞保持在体外增加迁移率,在p75 NGFR裸小鼠中检测到的分布变化一致。慢性抑制p75 NGFR引起嗅觉轴突成束的衰减和OEC密度的降低,再次模仿在无效小鼠中检测到的变化。然而,长期给药后发现GnRH细胞数量减少,而在KO动物中未观察到,表明体外长期给药期间发生间接变化和/或体内发生代偿机制,可防止p75 NGFR缺失时GnRH神经元丢失。
Temporal and spatial localization of nerve growth factor receptor (p75NGFR) in the developing olfactory system and gonadotropin-releasing hormone-1 (GnRH) system was characterized and its role analyzed using p75NGFR null mice and nasal explants. Prenatally, p75NGFR was expressed by GnRH neurons and olfactory ensheathing cells (OECs). In p75NGFR null mice, no change in the number of GnRH cells was detected as compared to wild-type. However, in null mice, a shift in the distribution of GnRH neurons was found, with a small population of GnRH cells migrating further caudally toward the median eminence. Additionally, a reduction of both GAD67 positive olfactory axons and GFAP positive OEC fibers occurred. Acute administration of a p75NGFR blocker to GnRH cells maintained in vitro increased migration rate, consistent with the change in distribution detected in p75NGFR null mice. Chronic inhibition of p75NGFR caused an attenuation of olfactory axon fasciculation and a decrease in OEC density, again mimicking the changes detected in null mice. However, a reduction in GnRH cell number was found after chronic treatment that not observed in KO animals suggesting indirect changes occur during chronic treatment in vitro and/or a compensatory mechanism occurs in vivo that prevents loss of GnRH neurons in the absence of p75NGFR.
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