Influences of neurotrophins on mammalian motoneurons in vivo.
Influences of neurotrophins on mammalian motoneurons in vivo.
复制标题
神经营养素对体内哺乳动物运动神经元的影响。
DOI：
10.1002/neu.480241202
复制
发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Snider,WD
中科院分区：
文献类型：
--
作者：
Yan,Q;Elliott,JL;Matheson,C;Sun,J;Zhang,L;Mu,X;Rex,KL;Snider,WD
最近报道的几项研究表明，神经生长因子的神经营养蛋白家族的成员，脑源性神经营养因子（BDNF），在体外支持运动神经元，并将运动神经元从自然发生的和轴突切断诱导的细胞死亡中拯救出来（Oppenheim等人，1992 b; Sendtner等人，1992 b; Yan等人，1992; Koliatsos等人，1993;亨德森等人，1993年）。在目前的研究中，我们探讨了BDNF和其他神经营养因子是否在发育过程中调节运动神经元的存活，并询问运动神经元递质酶的合成是否也受到调节。我们首先研究了新生动物的脊髓运动神经元是否能以特异性受体介导的方式从其靶点逆行转运碘化神经营养因子。我们发现，运动神经元很容易运输NGF，BDNF和神经营养素-3（NT-3）。过量的未标记同源因子可完全或大部分阻断一种因子的逆行转运，而过量的未标记异源因子仅部分阻断一种因子的逆行转运。由于以前的研究表明，这三种神经营养因子结合低亲和力的神经生长因子受体，p75 NGFR，具有相似的亲和力，我们的数据表明，逆行运输的神经营养因子运动神经元可能介导的额外的组件，如trk家族的原癌基因。与这一假设相一致，我们在这里证明，运动神经元表达mRNA的两个成员的trk家族，trkB和trkC。此外，trkB和trkC都由E13表达，这与BDNF和NT-3在调节涉及运动神经元的重要发育事件（如自然发生的细胞死亡）中的作用一致。为了确定神经营养因子家族的哪些成员影响运动神经元的存活并评估其作用的一般性，我们评估了NGF、BDNF和NT-3在新生儿轴突切断术后挽救脊髓和颅运动神经元的能力。局部应用BDNF保存了40-70%的运动神经元，这些运动神经元通常会在腰和颅运动池的轴突切断术后死亡，这取决于所采用的治疗方案。NT-3还表现出一定的拯救运动神经元的能力，并挽救了20-25%的运动神经元，这些运动神经元在没有治疗的情况下会死亡。最后，我们询问神经营养因子是否可以影响运动神经元的递质酶的合成以及它们在轴突切断后的存活。局部应用BDNF和NT-3可部分防止坐骨神经切断后L4和L5前根蛋白质含量的减少。然而，这些神经营养因子的治疗并没有阻止胆碱乙酰转移酶（ChAT）活性的下降，在L4和L5腹根，这是由于这个程序。这些结果表明，BDNF和NT-3是在体内调节运动神经元发育的生长因子之一，但它们的作用可能比原型因子NGF对其反应神经元的作用更受限制。
Several recently reported investigations have shown that a member of the neurotrophin family of neuronal growth factors, brain-derived neurotrophic factor (BDNF), supports motoneurons in vitro and rescues motoneurons from naturally occurring and axotomy-induced cell death (Oppenheim et al., 1992b; Sendtner et al., 1992b; Yan et al., 1992; Koliatsos et al., 1993; Henderson et al., 1993). In the current study, we have explored the issue of whether BDNF and other neurotrophins act to regulate motoneuron survival during development and asked whether synthesis of motoneuron transmitter enzymes is also regulated. We first examined whether spinal motoneurons in newborn animals could retrogradely transport iodinated neurotrophins from their targets in a specific, receptor-mediated manner. We found that motoneurons readily transported NGF, BDNF, and neurotrophin-3 (NT-3). The retrograde transport of one factor could be completely or largely blocked by excess of unlabeled homologous factor, but only partially blocked by excess of unlabeled heterologous factors. Since previous studies have shown that these three neurotrophins bind to the low-affinity NGF receptor, p75 NGFR, with similar affinity, our data suggest that the retrograde transport of neurotrophins by motoneurons may be mediated by additional components, such as the trk family of proto-oncogenes. Consistent with this hypothesis, we demonstrate here that motoneurons express mRNA for two members of the trk family, trkB and trkC. Furthermore, both trkB and trkC were expressed by E13, consistent with a role for BDNF and NT-3 in regulating important developmental events involving motoneurons such as naturally occurring cell death. In order to determine which members of the neurotrophin family influence motoneuron survival and to assess the generality of their effects, we evaluated the abilities of NGF, BDNF, and NT-3 to save both spinal and cranial motoneurons after neonatal axotomy. Locally applied BDNF saved 40–70% of motoneurons which would ordinarily die after axotomy in lumbar and cranial motor pools, depending on the treatment protocol employed. NT-3 also exhibited some ability to rescue motoneurons and saved 20–25% of motoneurons which would die in the absence of treatment. Finally, we asked whether neurotrophins could influence synthesis of transmitter enzymes by motoneurons as well as their survival after axotomy. Locally applied BDNF and NT-3 could partially prevent the decrease of protein contents in L 4 and L 5 ventral roots which normally follows sciatic nerve transection. However, treatment with these neurotrophins did not prevent the decrease in choline acetyltransferase (ChAT) activity in L 4 and L 5 ventral roots which results from this procedure. These results suggest that BDNF and NT-3 are among the growth factors that regulate motoneuron development in vivo, but that their actions may be more restricted than those of the prototypical factor, NGF, on its responsive neurons.© 1993 John Wiley & Sons, Inc.
登录
查看更多内容
神经营养素 BDNF、NT-3 和 NT-4/5（而非 NGF）上调发育中运动神经元的胆碱能表型
影响因子：
3.4
作者：
V. Wong;Ruth Arriaga;N. Ip;R. Lindsay
通讯作者：
R. Lindsay
大鼠球海绵体脊髓核神经元大小的目标依赖性激素控制
影响因子：
2.9
作者：
I. Araki;Y. Harada;M. Kuno
通讯作者：
M. Kuno
影响因子：
--
作者：
Hamburger, V
通讯作者：
Hamburger, V
具有不同功能的大鼠 TrkC 的替代形式
影响因子：
16.2
作者：
D. Valenzuela;P. Maisonpierre;D. Glass;E. Rojas;L. Nuñez;Yuan Kong;D. Gies;T. Stitt;N. Ip;G. Yancopoulos
通讯作者：
G. Yancopoulos
DOI：
--
发表时间：
1982
期刊：
The Journal of comparative neurology
影响因子：
--
作者：
R. Oppenheim;J. Maderdrut;D. Wells
通讯作者：
D. Wells