Functional Evidence that BDNF Is an Anterograde Neuronal Trophic Factor in the CNS
Functional Evidence that BDNF Is an Anterograde Neuronal Trophic Factor in the CNS
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BDNF 是中枢神经系统顺行神经元营养因子的功能证据
DOI：
10.1523/jneurosci.18-08-02808.1998
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
F. Miller
中科院分区：
文献类型：
--
作者：
J. P. Fawcett;S. Bamji;C. G. Causing;R. Aloyz;A. Ase;T. Reader;J. McLean;F. Miller
在这份报告中，我们已经测试的假设，脑源性神经营养因子（BDNF）是一种顺行性神经营养因子在中枢神经系统，并集中在中枢去甲肾上腺素能神经元合成BDNF。BDNF和多巴胺-β-羟化酶（DBH）的双标记免疫细胞化学研究表明，BDNF在成年大鼠脑内部分定位于去甲肾上腺素能神经纤维和终末。为了测试这种顺行BDNF的功能重要性，我们分析了携带DBH-BDNF小基因的转基因小鼠。DBH-BDNF小鼠的去甲肾上腺素能神经元中BDNF合成的增加在整个出生后生活中引起新皮质（去甲肾上腺素能靶区域）中TrkB酪氨酸激酶活化升高。这种传入调节TrkB受体活性的增加导致皮质形态的长期改变。为了确定是否去甲肾上腺素能神经元表达的BDNF也顺行调节神经元的存活，我们研究了第二个去甲肾上腺素能靶，新生儿面部运动神经元。轴突切断后一周，对照组动物中72%的面运动神经元丢失，而DBH-BDNF转基因小鼠中仅丢失30-35%。总之，这些结果表明，BDNF是顺行运输的纤维和终端的去甲肾上腺素能神经元，顺行分泌的BDNF导致激活的TrkB在目标地区，这种分泌有功能的后果，目标神经元的生存和分化。这种BDNF的突触前分泌可能提供了一种调节神经回路的细胞机制，无论是在发育中还是在成熟的神经系统中。
In this report, we have tested the hypothesis that brain-derived neurotrophic factor (BDNF) is an anterograde neurotrophic factor in the CNS and have focused on central noradrenergic neurons that synthesize BDNF. Double-label immunocytochemistry for BDNF and dopamine-β-hydroxylase (DBH), a marker for noradrenergic neurons, demonstrated that BDNF is partially localized to noradrenergic nerve fibers and terminals in the adult rat brain. To test the functional importance of this anterograde BDNF, we analyzed transgenic mice carrying a DBH–BDNF minigene. Increased synthesis of BDNF in noradrenergic neurons of DBH–BDNF mice caused elevated TrkB tyrosine kinase activation throughout postnatal life in the neocortex, a noradrenergic target region. This afferently regulated increase in TrkB receptor activity led to long-lasting alterations in cortical morphology. To determine whether noradrenergic neuron-expressed BDNF also anterogradely regulated neuronal survival, we examined a second noradrenergic target, neonatal facial motoneurons. One week after axotomy, 72% of facial motoneurons were lost in control animals, whereas only 30–35% were lost in DBH–BDNF transgenic mice. Altogether, these results indicate that BDNF is anterogradely transported to fibers and terminals of noradrenergic neurons, that anterogradely secreted BDNF causes activation of TrkB in target regions, and that this secretion has functional consequences for target neuron survival and differentiation. This presynaptic secretion of BDNF may provide a cellular mechanism for modulating neural circuitry, in either the developing or mature nervous system.
影响因子：
56.9
作者：
GHOSH, A;CARNAHAN, J;GREENBERG, ME
通讯作者：
GREENBERG, ME