Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
J Neurosci. 2010 Feb 3;30(5):1739-49. doi: 10.1523/JNEUROSCI.5100-09.2010.
Although brain-derived neurotrophic factor (BDNF) is linked with an increasing number of conditions causing brain dysfunction, its role in the postnatal CNS has remained difficult to assess. This is because the bdnf-null mutation causes the death of the animals before BDNF levels have reached adult levels. In addition, the anterograde axonal transport of BDNF complicates the interpretation of area-specific gene deletion. The present study describes the generation of a new conditional mouse mutant essentially lacking BDNF throughout the CNS. It shows that BDNF is not essential for prolonged postnatal survival, but that the behavior of such mutant animals is markedly altered. It also reveals that BDNF is not a major survival factor for most CNS neurons and for myelination of their axons. However, it is required for the postnatal growth of the striatum, and single-cell analyses revealed a marked decreased in dendritic complexity and spine density. In contrast, BDNF is dispensable for the growth of the hippocampus and only minimal changes were observed in the dendrites of CA1 pyramidal neurons in mutant animals. Spine density remained unchanged, whereas the proportion of the mushroom-type spine was moderately decreased. In line with these in vivo observations, we found that BDNF markedly promotes the growth of cultured striatal neurons and of their dendrites, but not of those of hippocampal neurons, suggesting that the differential responsiveness to BDNF is part of a neuron-intrinsic program.
尽管脑源性神经营养因子（BDNF）与越来越多导致大脑功能障碍的疾病有关，但它在出生后中枢神经系统中的作用仍然难以评估。这是因为 bdnf 基因敲除突变会导致动物在 BDNF 水平达到成年水平之前死亡。此外，BDNF 的顺行轴突运输使特定区域基因缺失的解释变得复杂。本研究描述了一种新型条件性小鼠突变体的产生，该突变体基本上在整个中枢神经系统中缺乏 BDNF。研究表明，BDNF 对于延长出生后的存活并非必需，但此类突变动物的行为明显改变。研究还表明，BDNF 不是大多数中枢神经系统神经元及其轴突髓鞘形成的主要生存因素。然而，BDNF 对于纹状体的出生后生长是必需的，单细胞分析显示树突复杂性和棘突密度明显降低。相比之下，BDNF 对于海马体的生长是可有可无的，在突变动物的 CA1 锥体神经元的树突中仅观察到微小变化。棘突密度保持不变，而蘑菇状棘突的比例适度降低。与这些体内观察结果一致，我们发现 BDNF 显著促进培养的纹状体神经元及其树突的生长，但不促进海马神经元的生长，这表明对 BDNF 的不同反应是神经元内在程序的一部分。
