Brain-derived neurotrophic factor signaling does not stimulate subventricular zone neurogenesis in adult mice and rats.
Brain-derived neurotrophic factor signaling does not stimulate subventricular zone neurogenesis in adult mice and rats.
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DOI：
10.1523/jneurosci.2918-08.2008
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发表时间：
2008-12-10
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影响因子：
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通讯作者：
Alvarez-Buylla A
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作者：
Galvão RP;Garcia-Verdugo JM;Alvarez-Buylla A
在啮齿类动物中，成年心室下区（SVZ）产生神经母细胞，这些神经母细胞迁移到嗅球（OB）并分化为中间神经元。最近的研究表明，神经营养因子脑源性神经营养因子（BDNF）可以促进成人SVZ神经发生，但其作用机制尚不清楚。在此，我们分析了BDNF及其受体TrkB在成人SVZ神经发生中的作用。我们发现TrkB是小鼠SVZ中最突出的神经营养因子受体，但只检测到截断的激酶阴性亚型（TrkB- tr）。TrkB-TR在SVZ星形细胞和室管膜细胞中表达，但在神经母细胞中不表达。TrkB突变体降低SVZ的增殖和存活，减少新的OB神经元。为了测试这种效应是否具有细胞自主性，我们将TrkB敲除小鼠（TrkB- ko）的SVZ细胞移植到野生型小鼠（WT）的SVZ中。移植物祖细胞产生的神经母细胞在缺乏TrkB的情况下迁移到OB。颗粒状中间神经元和Calbindin+的肾小球周围神经元的存活和分化似乎不受TrkB缺失的影响，而多巴胺能的肾小球周围神经元则减少。脑室内灌注BDNF产生的结果因动物种类而异，对小鼠SVZ神经元的产生没有影响，而对大鼠SVZ神经元的产生则有所减少。有趣的是，小鼠和大鼠在神经营养因子受体p75的表达上也有所不同。我们的研究结果表明，TrkB不是成人SVZ神经发生所必需的，也不支持目前认为将BDNF输送到SVZ可以促进成人神经发生的观点。
In rodents, the adult subventricular zone (SVZ) generates neuroblasts which migrate to the olfactory bulb (OB) and differentiate into interneurons. Recent work suggests that the neurotrophin Brain-Derived Neurotrophic Factor (BDNF) can enhance adult SVZ neurogenesis, but the mechanism by which it acts is unknown. Here, we analyzed the role of BDNF and its receptor TrkB in adult SVZ neurogenesis. We found that TrkB is the most prominent neurotrophin receptor in the mouse SVZ, but only the truncated, kinase-negative isoform (TrkB-TR) was detected. TrkB-TR is expressed in SVZ astrocytes and ependymal cells, but not in neuroblasts. TrkB mutants have reduced SVZ proliferation and survival and fewer new OB neurons. To test if this effect is cell-autonomous, we grafted SVZ cells from TrkB knockout mice (TrkB-KO) into the SVZ of wild-type mice (WT). Grafted progenitors generated neuroblasts that migrated to the OB in the absence of TrkB. The survival and differentiation of granular interneurons and Calbindin+ periglomerular interneurons seemed unaffected by the loss of TrkB, while dopaminergic periglomerular neurons were reduced. Intra-ventricular infusion of BDNF yielded different results depending on the animal species, having no effect on neuron production from mouse SVZ, while decreasing it in rats. Interestingly, mice and rats also differ in their expression of the neurotrophin receptor, p75. Our results indicate that TrkB is not essential for adult SVZ neurogenesis and do not support the current view that delivering BDNF to the SVZ can enhance adult neurogenesis.