Leingärtner A, Heisenberg C P, Kolbeck R, Thoenen H, Lindholm D
Department of Neurochemistry, Max Planck Institute for Psychiatry, Martinsried, Germany.
J Biol Chem. 1994 Jan 14;269(2):828-30.
Neurotrophin-3 (NT-3) is a member of the neurotrophin gene family and is highly expressed in the developing rat cerebellum. Here we show that brain-derived neurotrophic factor (BDNF) increased by approximately 10-fold the NT-3 mRNA levels in cultured cerebellar granule neurons isolated from postnatal rats, whereas nerve growth factor (NGF) and NT-3 itself had no effect. The effect of BDNF was additive to that of triiodothyronine (T3), which also increased NT-3 mRNA in these neurons. The drug K252a inhibited the BDNF-mediated stimulation of NT-3 expression, suggesting an involvement of trkB receptors. Nuclear run-on experiments showed that BDNF enhanced NT-3 transcription, whereas the stability of NT-3 mRNA remained unchanged. The data presented are the first demonstration that one neurotrophin regulates the expression of another and provide evidence that NT-3 production in granule neurons is regulated by both BDNF and T3.
神经营养因子-3（NT-3）是神经营养因子基因家族的成员之一，在发育中的大鼠小脑中高度表达。在此我们表明，脑源性神经营养因子（BDNF）可使从新生大鼠分离的培养小脑颗粒神经元中的NT-3 mRNA水平增加约10倍，而神经生长因子（NGF）和NT-3本身则无此作用。BDNF的作用与三碘甲状腺原氨酸（T3）的作用具有相加性，T3也可增加这些神经元中的NT-3 mRNA。药物K252a抑制了BDNF介导的NT-3表达刺激，提示trkB受体参与其中。细胞核转录实验表明，BDNF增强了NT-3转录，而NT-3 mRNA的稳定性保持不变。所呈现的数据首次证明一种神经营养因子可调节另一种神经营养因子的表达，并提供了颗粒神经元中NT-3产生受BDNF和T3两者调节的证据。
