Brain-derived neurotrophic factor signaling in the HVC is required for testosterone-induced song of female canaries.
Brain-derived neurotrophic factor signaling in the HVC is required for testosterone-induced song of female canaries.
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DOI：
10.1523/jneurosci.2564-09.2009
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发表时间：
2009-12-09
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影响因子：
--
通讯作者：
Gahr M
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作者：
Hartog TE;Dittrich F;Pieneman AW;Jansen RF;Frankl-Vilches C;Lessmann V;Lilliehook C;Goldman SA;Gahr M
在鸣禽中，睾酮诱导的鸣叫被认为涉及睾酮依赖的形态变化，包括血管生成和神经元重新进入HVC，HVC是歌唱控制电路的中心部分。以往的研究表明，睾酮可诱导血管内皮生长因子(VEGF)及其受体(VEGFR2酪氨酸激酶)的产生，进而导致HVC内皮细胞脑源性神经营养因子(BDNF)的产生上调。在这里，我们首次报道，尽管持续的雄激素暴露和睾酮对HVC形态的持续影响，全身性抑制VEGFR2酪氨酸激酶足以阻断睾酮诱导的成年雌性金丝雀的鸣叫。通过原位转染法在HVC中表达外源BDNF，逆转了VEGFR2抑制介导的SONG发育的阻断，从而恢复了雄激素诱导的SONG相关的行为表型。被VEGFR2抑制，接受BDNF治疗的雌性产生了精心制作的类似男性的歌曲，包括大型音节曲目和高音节重复率，这是众所周知吸引雌性的特征。重要的是，尽管在睾酮治疗后，HVC招募到了功能正常的新神经元，但神经元增加的时间进程似乎遵循BDNF诱导的SING发育。这些发现表明，雄激素诱导的成年鸣禽鸣叫需要与睾酮相关的VEGFR2活性，BDNF可以挽救成年HVC内VEGFR2抑制的行为效应。
Testosterone-induced singing in songbirds is thought to involve testosterone-dependent morphological changes that include angiogenesis and neuronal recruitment into the HVC, a central part of the song control circuit. Previous work showed that testosterone induces the production of vascular endothelial growth factor (VEGF) and its receptor (VEGFR2 tyrosine kinase), which in turn leads to an upregulation of brain-derived neurotrophic factor (BDNF) production in HVC endothelial cells. Here we report for the first time that systemic inhibition of the VEGFR2 tyrosine kinase is sufficient to block testosterone-induced song in adult female canaries, despite sustained androgen exposure and the persistence of the effects of testosterone on HVC morphology. Expression of exogenous BDNF in HVC, induced locally by in situ transfection, reversed the VEGFR2 inhibition-mediated blockade of song development, thereby restoring the behavioral phenotype associated with androgen-induced song. The VEGFR2-inhibited, BDNF-treated females developed elaborate male-like song that included large syllable repertoires and high syllable repetition rates, features known to attract females. Importantly, although functionally competent new neurons were recruited to HVC after testosterone treatment, the time course of neuronal addition appeared to follow BDNF-induced song development. These findings indicate that testosterone-associated VEGFR2 activity is required for androgen-induced song in adult songbirds and that the behavioral effects of VEGFR2 inhibition can be rescued by BDNF within the adult HVC.