脑源性神经营养因子在体内对视网膜神经节细胞的树突和轴突分支有不同的调节作用。
Brain-derived neurotrophic factor differentially regulates retinal ganglion cell dendritic and axonal arborization in vivo.
作者信息
Lom B, Cohen-Cory S
机构信息
Mental Retardation Research Center, Departments of Psychiatry and Neurobiology, University of California, Los Angeles, Los Angeles, California 90025, USA.
出版信息
J Neurosci. 1999 Nov 15;19(22):9928-38. doi: 10.1523/JNEUROSCI.19-22-09928.1999.
Expression of the neurotrophin brain-derived neurotrophic factor (BDNF) and its receptor trkB in the ganglion cell layer of the Xenopus retina during retinal ganglion cell (RGC) dendritic arborization indicates that BDNF is spatially and temporally available to influence RGC morphological differentiation (; ). BDNF promotes RGC axon arborization in vivo by acting as a target-derived trophic factor (). To determine whether BDNF also acts locally to regulate RGC dendritic development in vivo, we altered retinal neurotrophin levels at the onset of dendritic arborization and assessed the resulting arbor morphologies of RGCs retrogradely labeled with fluorescent dextrans. Injecting neurotrophins or BDNF function-blocking antibodies coupled to microspheres provided local alterations of retinal neurotrophin levels. BDNF significantly decreased RGC dendritic arbor complexity, whereas neutralizing endogenous BDNF levels with function-blocking antibodies significantly increased dendritic arbor complexity. RGCs exposed to other neurotrophins, as well as RGCs in retinae treated with BDNF but in areas not directly exposed to the neurotrophin, developed dendritic arbors that were indistinguishable from controls, indicating that exogenous BDNF acts specifically and locally. In the tectum, where RGC axons arborize, BDNF had opposite effects. BDNF significantly increased RGC axon arbor complexity and anti-BDNF reduced RGC arborization. Thus, BDNF reduces RGC dendritic arborization within the retina and increases axon arborization in the tectum. These results indicate that BDNF can differentially modulate axonal and dendritic arborization within a single neuronal population in opposing manners and raise the possibility that differential modulation by a neurotrophic factor finely tunes the morphological differentiation program of a neuron.
在视网膜神经节细胞(RGC)树突分支形成过程中,神经营养因子脑源性神经营养因子(BDNF)及其受体trkB在非洲爪蟾视网膜神经节细胞层中的表达表明,BDNF在空间和时间上都可用于影响RGC的形态分化(;)。BDNF作为一种靶源性营养因子,在体内促进RGC轴突分支形成()。为了确定BDNF在体内是否也通过局部作用来调节RGC树突发育,我们在树突分支形成开始时改变视网膜神经营养因子水平,并评估用荧光葡聚糖逆行标记的RGC的树突形态。将神经营养因子或与微球偶联的BDNF功能阻断抗体注射到视网膜中,可局部改变视网膜神经营养因子水平。BDNF显著降低了RGC树突分支的复杂性,而用功能阻断抗体中和内源性BDNF水平则显著增加了树突分支的复杂性。暴露于其他神经营养因子的RGC,以及用BDNF处理但未直接暴露于该神经营养因子区域的视网膜中的RGC,其形成的树突分支与对照组无明显差异,这表明外源性BDNF具有特异性的局部作用。在RGC轴突分支形成的顶盖中,BDNF具有相反的作用。BDNF显著增加了RGC轴突分支的复杂性,而抗BDNF则减少了RGC的分支形成。因此,BDNF减少视网膜内RGC的树突分支形成,增加顶盖中轴突的分支形成。这些结果表明,BDNF可以以相反的方式差异性地调节单个神经元群体内的轴突和树突分支形成,并增加了神经营养因子的差异性调节精细调整神经元形态分化程序的可能性。