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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Testosterone-induced matrix metalloproteinase activation is a checkpoint for neuronal addition to the adult songbird brain.
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Testosterone-induced matrix metalloproteinase activation is a checkpoint for neuronal addition to the adult songbird brain.

机译：睾丸激素诱导的基质金属蛋白酶激活是成年鸣禽大脑神经元添加的检查点。

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Testosterone-induced neuronal addition to the adult songbird vocal control center, HVC, requires the androgenic induction of vascular endothelial growth factor (VEGF), followed by VEGF-stimulated angiogenesis. The expanded vasculature acts as a source of BDNF, which supports the immigration of new neurons from the overlying ventricular zone. In tumorigenesis, a similar process of adult angiogenesis is regulated by matrix metalloproteinase (MMP) activity, in particular that of the gelatinases. We therefore investigated the role of the gelatinases in neuronal addition to the HVC of adult female canaries. In situ zymography of the caudal forebrain revealed that testosterone-induced perivascular gelatinase activity that was most prominent in HVC. High-resolution gels revealed distinct MMP activities that comigrated with MMP2 and MMP9, and PCR cloning yielded MMP2 and MMP9 orthologues of 1465 and 1044 bp, respectively. Quantitative PCR revealed that HVC MMP2 mRNA levels doubled within 8 d of testosterone, whereas MMP9 transcript levels were stable. Moreover, isolated adult canary forebrain endothelial cells secreted MMP2, and VEGF substantially increased endothelial MMP2 gelatinase activity. To assess the importance of androgen-regulated, VEGF-induced MMP2 to adult angiogenesis and neurogenesis, we treated testosterone-implanted females with the gelatinase inhibitor SB-3CT. In situ zymography confirmed that SB-3CT suppressed gelatinase activity in HVC, and histological analysis revealed that SB-3CT-treated birds exhibited a decreased endothelial mitotic index and substantially diminished neuronal recruitment to HVC. These data suggest that the androgenic induction of endothelial MMP2 is a critical regulator of neuronal addition to the adult HVC, and as such comprises an important regulatory step in adult neurogenesis.
机译：睾丸激素诱导的神经元添加到成年歌手的声音控制中心HVC中，需要雄激素诱导血管内皮生长因子（VEGF），然后是VEGF刺激的血管生成。扩张的脉管系统充当BDNF的来源，它支持新的神经元从上覆心室区的迁移。在肿瘤发生中，基质金属蛋白酶（MMP）的活性，特别是明胶酶的活性，调节着成人血管生成的类似过程。因此，我们调查了明胶酶在成年雌性金丝雀HVC的神经元添加中的作用。尾部前脑的原位酶谱显示，睾丸激素诱导的血管周明胶酶活性在HVC中最为突出。高分辨率凝胶揭示了与MMP2和MMP9竞争的独特的MMP活性，PCR克隆分别产生了1465和1044 bp的MMP2和MMP9直向同源物。定量PCR显示HVC MMP2 mRNA水平在睾丸激素的8 d内翻了一番，而MMP9转录水平是稳定的。此外，分离的成年金丝雀前脑内皮细胞分泌MMP2，而VEGF则显着增加了内皮MMP2明胶酶的活性。为了评估雄激素调节的，VEGF诱导的MMP2对成年血管生成和神经发生的重要性，我们用明胶酶抑制剂SB-3CT处理了植入睾丸激素的雌性。原位酶谱证实SB-3CT抑制了HVC中的明胶酶活性，并且组织学分析显示，经SB-3CT处理的禽类的内皮细胞有丝分裂指数降低，神经元向HVC的募集显着减少。这些数据表明，内皮细胞MMP2的雄激素诱导是成年HVC神经元添加的关键调节剂，因此，它包括成年神经发生中的重要调节步骤。

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