Adult ciliary neurotrophic factor receptors help maintain facial motor neuron choline acetyltransferase expression in vivo following nerve crush.
Adult ciliary neurotrophic factor receptors help maintain facial motor neuron choline acetyltransferase expression in vivo following nerve crush.
复制标题
成年睫状神经营养因子受体有助于在神经挤压后在体内维持面部神经胆碱乙酰转移酶的表达。
DOI：
10.1002/cne.24126
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发表时间：
2017-04-01
期刊：
影响因子：
--
通讯作者：
MacLennan AJ
中科院分区：
文献类型：
--
作者：
Lee N;Rydyznski CE;Rasch MS;Trinh DS;MacLennan AJ
外源性睫状神经营养因子(CNTF)在多种模型中促进运动神经元的存活。它还通过体外运动神经元增加关键神经递质酶胆碱乙酰转移酶(ChAT)的表达，可能与其对其生存的影响无关。我们利用成年小鼠面神经挤压模型和CNTFRCNTFRα基因的成年性条件性破坏，直接研究了内源性α受体在不依赖发育功能的成年运动神经元存活和ChAT维持中所起的作用。我们此前已经证明，在成年型CNTFRα小鼠中，CRER基因结构的激活会耗尽大部分运动神经元(以及所有骨骼肌，如图所示)中的这一基本受体亚单位，但对完整或受损运动神经元的存活没有影响，从而表明这些成体CNTF受体在该模型中不起重要的生存作用，而不是它们在胚胎发育期间的重要作用。我们在这里表明，同样的CNTFRα缺失并不影响非受损运动神经元中ChAT的标记，但它显著增加了神经挤压后ChAT的丢失。这些数据表明，虽然运动神经元和肌肉CNTF受体在维持完整的成年运动神经元的ChAT中都不起到显著的、非冗余的作用，但当运动神经元受到神经挤压的挑战时，受体成为维持ChAT的关键。因此，这些数据表明，受体是内源性神经保护机制的关键组成部分。使用成人型CNTF受体阻断和小鼠面神经挤压模型，本研究表明成人型CNTF受体有助于维持受损运动神经元中关键神经递质酶胆碱乙酰转移酶的表达。图为右侧运动神经元胆碱乙酰转移酶免疫组织化学染色。
Exogenous ciliary neurotrophic factor (CNTF) administration promotes the survival of motor neurons in a wide range of models. It also increases the expression of the critical neurotransmitter enzyme, choline acetyltransferase (ChAT), by in vitro motor neurons, likely independent of its effects on their survival. We have used the adult mouse facial nerve crush model and adult onset conditional disruption of the CNTF receptor α (CNTFRα) gene to directly examine the in vivo roles played by endogenous CNTF receptors in adult motor neuron survival and ChAT maintenance, independent of developmental functions. We have previously shown that adult activation of the CreER gene construct in floxed CNTFRα mice depletes this essential receptor subunit in a large subset of motor neurons (and all skeletal muscle, as shown here) but has no effect on the survival of intact or lesioned motor neurons, thereby indicating that these adult CNTF receptors play no essential survival role in this model, in contrast to their essential role during embryonic development. We show here that this same CNTFRα depletion does not affect ChAT labeling in non-lesioned motor neurons, but it significantly increases the loss of ChAT following nerve crush. The data suggest that while neither motor neuron nor muscle CNTF receptors play a significant, non-redundant role in the maintenance of ChAT in intact adult motor neurons, the receptors become essential for ChAT maintenance when the motor neurons are challenged by nerve crush. Therefore, the data suggest that the receptors act as a critical component of an endogenous neuroprotective mechanism. Using adult onset CNTF receptor disruption and the mouse facial nerve crush model, this study shows that adult CNTF receptors help maintain expression of the critical neurotransmitter enzyme, choline acetyltransferase in lesioned motor neurons. Image shows choline acetyltransferase immunohistochemistry of motor neurons with the lesion side on the right.
影响因子：
2.5
作者：
Lee, Nancy;Rydyznski, Carolyn E.;Spearry, Rachel P.;Robitz, Rachel;MacLennan, A. John
通讯作者：
MacLennan, A. John