Expression of Glial Cell-Derived Neurotrophic Factor Receptors Within Nucleus Ambiguus During Rat Development.

Expression of Glial Cell-Derived Neurotrophic Factor Receptors Within Nucleus Ambiguus During Rat Development.
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DOI:
10.1002/lary.30440
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发表时间:
2023-09
期刊:
影响因子:
2.6
通讯作者:
Pitman, Michael J.
Pitman, Michael J.
中科院分区:
医学2区
文献类型:
--
作者:
Blount, Quinton;Hernandez-Morato, Ignacio;Moayedi, Yalda;Pitman, Michael J.

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疑核(NAmb)是延髓中参与延髓功能的神经元柱。在喉返神经(RLN)损伤后的神经再支配过程中,观察到GDNF及其受体(GDNFR)在细胞体内的表达。关于GDNFR在NAmb形成和胚胎发育过程中喉神经支配中的表达知之甚少。了解胚胎发生与喉返神经损伤后GDNFR表达的时间和模式可能为喉返神经损伤后再生的治疗靶点提供见解。实验室实验。对E14.5/E16.5/E18.5/E20.5/成年大鼠脑干进行GDNFR染色:GFRα-1/GFRα-2/GFRα-3/Ret。Islet 1和ChAT被用作细胞体标记物。使用荧光显微镜观察切片,并通过手动细胞计数进行定量。GFRα-1、GFRα-3和Ret的表达在成人延髓的NAmb、舌下神经和面神经核中被鉴定。在发育过程中,在E20.5时观察到GFRα-1免疫反应性。在任何时间点均未观察到GFRα-2表达。GFRα-3表达开始于E16.5。从E14.5开始观察到NAmb中神经纤维内的Ret表达,但从未在细胞体中表达。喉返神经损伤后,胚胎NAmb中的GDNFR表达与成人不同。发育中的脑干在离散的时间点经历了上调,信号持续到成年。相反,成年RLN横断大鼠经历了上调和下调模式。GFRα-1可能有助于肌肉靶向和NMJ成熟,GFRα-3可能有助于两者以及轴突导向。GDNF很可能通过不依赖于Ret的途径发挥作用。当GDNF受体在神经元中表达时,GDNF参与肌肉神经支配。神经损伤后,胚胎喉神经支配与成人喉神经再支配过程中GNDF受体表达不同。它可能是声带麻痹的一种治疗选择。
The nucleus ambiguus (NAmb) is a column of neurons, in the medulla oblongata, involved in bulbar functions. Expression of GDNF and its receptors (GDNFR) are observed within the cell bodies during reinnervation following recurrent laryngeal nerve (RLN) injury. Little is known regarding GDNFR expression in the formation of the NAmb and the laryngeal innervation during embryogenesis. Understanding the timing and pattern of GDNFR expression in embryogenesis versus after RLN injury may provide insights into therapeutic targets for regeneration after RLN injury. Laboratory experiment. Rat brainstems at E14.5/E16.5/E18.5/E20.5/adult were stained for GDNFR: GFRα-1/GFRα-2/GFRα-3/Ret. Islet1 and ChAT were used as cell bodies markers. Sections were observed using fluorescent microscopy and quantified through manual cell counting. Expression of GFRα-1, GFRα-3, and Ret was identified within the NAmb, hypoglossal and facial nuclei of the adult medulla. During development, GFRα-1 immunoreactivity was seen at E20.5. GFRα-2 expression was not observed at any timepoint. GFRα-3 expression began at E16.5. Ret expression within nerve fibers in the NAmb were observed beginning at E14.5, but never in the cell bodies. Embryonic GDNFR expression in the NAmb differs from that of the adult after RLN injury. The developing brainstem experienced upregulation at discrete timepoints with signaling sustained through adulthood. In contrast, adult RLN transected rats experienced patterns of up and down regulation. GFRα-1 may contribute to muscle targeting and NMJ maturation, GFRα-3 may contribute to both, as well as axon guidance. It is likely that GDNF is functioning via a Ret-independent pathway. GDNF participates in muscle innervation when its receptors are expressed in neurons. GNDF Receptors expression are different during innervation of the larynx in embryos versus reinnervation in adults after nerve injury. It may be a therapeutic option for vocal fold paralysis.
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