The contribution of ciliary neurotrophic factor receptors to adult motor neuron survival in vivo is specific to insult type and distinct from that for embryonic motor neurons.
The contribution of ciliary neurotrophic factor receptors to adult motor neuron survival in vivo is specific to insult type and distinct from that for embryonic motor neurons.
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DOI：
10.1002/cne.23341
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发表时间：
2013-10-01
影响因子：
2.5
通讯作者：
MacLennan, A. John
中科院分区：
文献类型：
--
作者：
Lee, Nancy;Rydyznski, Carolyn E.;Spearry, Rachel P.;Robitz, Rachel;MacLennan, A. John
外源性睫状神经营养因子（CNTF）促进创伤后运动神经元（MN）存活和MN疾病的遗传模型。小鼠CNTF受体α（CNTFRα）基因的无条件破坏导致MN损失，表明内源性CNTF受体信号传导的发育作用。这些数据还表明，CNTF受体可以促进成年MN存活，适当地操纵受体可以有效地治疗成年MN疾病。这项工作将大大受益于更好地了解CNTF受体在成年MN中所发挥的作用。我们先前已经发现，通过AAV-Cre载体注射，“floxed CNTFRα”小鼠面部MN中CNTFRα的成年发作破坏导致比相同处理的对照组显著更多的MN损失。虽然表明CNTF受体可以促进成年MN存活，但数据没有区分MN维持中的潜在作用与保护MN免受注射相关创伤或由AAV-Cre产生的慢性Cre重组酶（Cre）的毒性的作用。在这里，我们使用了一种诱导型Cre基因构建体，在面部MN中产生成人发病的CNTFRα破坏，而没有AAV-Cre程序的创伤和毒性作用。MN在没有CNTFRα的情况下存活，即使受到面神经挤压或注射相关创伤的挑战，从而表明，与我们先前的研究相结合，内源性CNTF受体信号传导可以保护MN免受毒性损伤，例如慢性Cre产生的毒性损伤。这些数据还表明，在体内CNTF受体发挥非常不同的作用，在成人和胚胎MNs。
Exogenous ciliary neurotrophic factor (CNTF) promotes motor neuron (MN) survival following trauma and in genetic models of MN disease. Unconditional disruption of the mouse CNTF receptor α (CNTFRα) gene leads to MN loss, demonstrating a developmental role for endogenous CNTF receptor signaling. These data also suggest that CNTF receptors may promote adult MN survival and that appropriately manipulating the receptors could effectively treat adult MN disorders. This effort would greatly benefit from a better understanding of the roles played by CNTF receptors in adult MNs. We have previously found that adult onset disruption of CNTFRα in facial MNs of “floxed CNTFRα” mice by AAV-Cre vector injection leads to significantly more MN loss than in identically treated controls. While indicating that CNTF receptors can promote adult MN survival, the data did not distinguish between potential roles in MN maintenance versus roles in protecting MNs from the injection associated trauma or the toxicity of the chronic Cre recombinase (Cre) produced by the AAV-Cre. Here we used an inducible Cre gene construct to produce adult-onset CNTFRα disruption in facial MNs without the traumatic and toxic effects of the AAV-Cre procedure. The MNs survive without CNTFRα, even when challenged by facial nerve crush or the injection-associated trauma, thereby suggesting, in conjunction with our previous study, that endogenous CNTF receptor signaling can protect MNs against toxic insult, such as that produced by chronic Cre. The data also indicate that in vivo CNTF receptors play very different roles in adult and embryonic MNs.
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影响因子：
64.5
作者：
DECHIARA, TM;VEJSADA, R;YANCOPOULOS, GD
通讯作者：
YANCOPOULOS, GD
影响因子：
1.5
作者：
Guo, CY;Yang, WY;Lobe, CG
通讯作者：
Lobe, CG
DOI：
10.1523/jneurosci.3386-12.2013
发表时间：
2013-01-16
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Lee N;Batt MK;Cronier BA;Jackson MC;Bruno Garza JL;Trinh DS;Mason CO;Spearry RP;Bhattacharya S;Robitz R;Nakafuku M;MacLennan AJ
通讯作者：
MacLennan AJ
DOI：
10.1073/pnas.93.20.10887
发表时间：
1996-10-01
影响因子：
11.1
作者：
Feil, R;Brocard, J;Chambon, P
通讯作者：
Chambon, P
DOI：
10.1097/00005072-199804000-00001
发表时间：
1998-04-01
影响因子：
3.2
作者：
Hyman, BT;Gomez-Isla, T;Irizarry, MC
通讯作者：
Irizarry, MC