The Neurotrophins BDNF, NT‐3 and NT‐4/5, But Not NGF, Up‐regulate the Cholinergic Phenotype of Developing Motor Neurons

The Neurotrophins BDNF, NT‐3 and NT‐4/5, But Not NGF, Up‐regulate the Cholinergic Phenotype of Developing Motor Neurons
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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

DOI:
10.1111/j.1460-9568.1993.tb00513.x
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发表时间:
1993
影响因子:
3.4
通讯作者:
R. Lindsay
R. Lindsay
中科院分区:
医学3区
文献类型:
--
作者:
V. Wong;Ruth Arriaga;N. Ip;R. Lindsay

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尽管发育中的运动神经元表达低亲和力神经生长因子 (NGF) 受体,但 NGF 对发育中或成年运动神经元的生物学效应尚不清楚。在这项研究中,我们发现,与 NGF 不同,脑源性神经营养因子 (BDNF)、神经营养蛋白-3 (NT-3) 和神经营养蛋白-4/5 (NT-4/5) 通过增加富含胚胎大鼠运动神经元的培养物中的胆碱乙酰转移酶 (CAT) 活性来刺激胆碱能表型。睫状神经营养因子 (CNTF) 也刺激 CAT 活性。 BDNF 和 NT-4/5 对 CAT 活性的影响似乎与 CNTF 具有协同作用。 BDNF 和 NT-3 共同治疗产生累加效应,表明信号转导是通过不同的高亲和力受体酪氨酸激酶 B 和 C(Trk B 和 Trk C)介导的。然而,与单独使用 BDNF 或 NT-4/5 相比,BDNF 和 NT-4/5 联合治疗并没有导致 CAT 活性增加,这表明它们的作用是通过相同的受体 Trk B 介导的。运动神经元富集培养物被发现表达 Trk B 和 Trk C 的 mRNA,这支持了我们的发现,即脊髓胆碱能神经元对神经营养素家族成员的营养作用有反应。分别为 BDNF 和 NT-4/5 和 NT-3 受体。
Although developing motor neurons express low‐affinity nerve growth factor (NGF) receptors, there is no known biological effect of NGF on developing or adult motor neurons. In this study, we found that, unlike NGF, brain‐derived neurotrophic factor (BDNF), neurotrophin‐3 (NT‐3) and neurotrophin‐4/5 (NT‐4/5) stimulated cholinergic phenotype by increasing choline acetyltransferase (CAT) activity in cultures enriched with embryonic rat motor neurons. Ciliary neurotrophic factor (CNTF) also stimulated CAT activity. The effects of BDNF and NT‐4/5 on CAT activity appeared to be synergistic with that of CNTF. Cotreatment with BDNF and NT‐3 resulted in an additive effect, suggesting that signal transduction was mediated through different high‐affinity receptors tyrosine kinases B and C (Trk B and Trk C). However, cotreatment with BDNF and NT‐4/5 did not result in an increase in CAT activity greater than that of either BDNF or NT‐4/5 alone, suggesting that their effects were mediated via the same receptor Trk B. Supporting our findings that spinal cholinergic neurons are responsive to trophic actions of members of the neurotrophin family, motor neuron‐enriched cultures were found to express mRNA for Trk B and Trk C, which have been identified as high‐affinity receptors for BDNF and NT‐4/5, and NT‐3, respectively.
刺激培养的脊髓神经元中胆碱乙酰转移酶活性的骨骼肌多肽的纯化。
DOI: --
发表时间: 1988
期刊: The Journal of biological chemistry
影响因子: --
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培养的脊髓神经元中胆碱能表达的调节。
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