Differential expression of mRNAs for neurotrophins and their receptors after axotomy of the sciatic nerve.
Differential expression of mRNAs for neurotrophins and their receptors after axotomy of the sciatic nerve.
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DOI：
10.1083/jcb.123.2.455
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发表时间：
1993-10
期刊：
影响因子：
--
通讯作者：
Persson H
中科院分区：
文献类型：
--
作者：
Funakoshi H;Frisén J;Barbany G;Timmusk T;Zachrisson O;Verge VM;Persson H
神经营养因子家族包括NGF、脑源性神经营养因子（BDNF）、神经营养因子-3 （NT-3）和神经营养因子-4 （NT-4）。先前的研究表明，在横断的坐骨神经远段的非神经元细胞中，NGF及其低亲和力受体的表达被诱导，这表明NGF在轴突再生过程中发挥了作用（Johnson, e.m., m.t aniuchi和p.s. DeStefano）。1988. 神经科学动态。11:299-304)。为了评估其他神经营养因子和Trk信号神经营养因子受体家族成员的作用，我们在此量化了成年大鼠坐骨神经横断后不同时间BDNF、NT-3和NT-4的mrna水平，以及trkA、trkB和trkC的mrna水平。病变2周后，坐骨神经远端段BDNF和NT-4 mrna明显升高。BDNF mRNA的增加是由BDNF外显子IV启动子的选择性激活介导的，肾上腺切除术使这种增加减少了50%。另一方面，NT-3 mRNA在横断后不久下降，但在2周后恢复到对照水平。在包裹坐骨神经的雪旺细胞中，在受损神经远端只检测到编码截断trkB受体的trkB mRNA，且水平降低。使用一种检测所有形式trkC mRNA的探针，也看到了类似的结果。在去神经腓肠肌中，BDNF mRNA水平升高，NT-3 mRNA水平不变，NT-4 mRNA水平下降。在脊髓中，仅观察到中性粒细胞和trk mrna水平的微小变化。这些结果表明，神经营养因子及其Trk受体mrna的表达在周围神经损伤后受到差异调节。基于这些结果，提出了不同神经营养因子如何协同促进损伤周围神经再生的模型。
The neurotrophin family includes NGF, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). Previous studies have demonstrated that expression of NGF and its low-affinity receptor is induced in nonneuronal cells of the distal segment of the transected sciatic nerve suggesting a role for NGF during axonal regeneration (Johnson, E. M., M. Taniuchi, and P. S. DeStefano. 1988. Trends Neurosci. 11:299-304). To assess the role of the other neurotrophins and the members of the family of Trk signaling neurotrophin receptors, we have here quantified the levels of mRNAs for BDNF, NT-3, and NT-4 as well as mRNAs for trkA, trkB, and trkC at different times after transection of the sciatic nerve in adult rats. A marked increase of BDNF and NT-4 mRNAs in the distal segment of the sciatic nerve was seen 2 wk after the lesion. The increase in BDNF mRNA was mediated by a selective activation of the BDNF exon IV promoter and adrenalectomy attenuated this increase by 50%. NT-3 mRNA, on the other hand, decreased shortly after the transection but returned to control levels 2 wk later. In Schwann cells ensheathing the sciatic nerve, only trkB mRNA encoding truncated TrkB receptors was detected with reduced levels in the distal part of the lesioned nerve. Similar results were seen using a probe that detects all forms of trkC mRNA. In the denervated gastrocnemius muscle, the level of BDNF mRNA increased, NT-3 mRNA did not change, while NT-4 mRNA decreased. In the spinal cord, only small changes were seen in the levels of neutrophin and trk mRNAs. These results show that expression of mRNAs for neurotrophins and their Trk receptors is differentially regulated after a peripheral nerve injury. Based on these results a model is presented for how the different neurotrophins could cooperate to promote regeneration of injured peripheral nerves.