Global Deprivation of Brain-Derived Neurotrophic Factor in the CNS Reveals an Area-Specific Requirement for Dendritic Growth
Global Deprivation of Brain-Derived Neurotrophic Factor in the CNS Reveals an Area-Specific Requirement for Dendritic Growth
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DOI：
10.1523/jneurosci.5100-09.2010
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发表时间：
2010-02-03
影响因子：
5.3
通讯作者：
Barde, Yves-Alain
中科院分区：
文献类型：
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作者：
Rauskolb, Stefanie;Zagrebelsky, Marta;Barde, Yves-Alain
虽然脑源性神经营养因子（BDNF）与越来越多的引起脑功能障碍的疾病有关，但其在出生后CNS中的作用仍然难以评估。这是因为BDNF无效突变导致动物在BDNF水平达到成年水平之前死亡。此外，BDNF的顺行轴突运输使区域特异性基因缺失的解释复杂化。本研究描述了一种新的条件突变小鼠的整个中枢神经系统基本上缺乏BDNF的一代。这表明BDNF对于延长出生后的存活时间并不是必需的，但这种突变动物的行为发生了显着改变。它还揭示了BDNF不是大多数CNS神经元及其轴突髓鞘形成的主要存活因子。然而，它是必要的出生后生长的纹状体，和单细胞分析表明，树突的复杂性和棘密度显着下降。与此相反，BDNF是海马生长的抑制剂，并且在突变动物的CA1锥体神经元树突中仅观察到最小的变化。棘密度保持不变，而蘑菇型棘的比例适度下降。与这些在体内的观察，我们发现，BDNF显着促进培养的纹状体神经元和树突的生长，但不是海马神经元，这表明对BDNF的差异反应是一个神经元的内在程序的一部分。
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.