In adult songbirds, the telencephalic song nucleus HVC and its efferent target RA undergo pronounced seasonal changes in morphology. In breeding birds, there are increases in HVC volume and total neuron number, and RA neuronal soma area compared to nonbreeding birds. At the end of breeding, HVC neurons die through caspase‐dependent apoptosis and thus, RA neuron size decreases. Changes in HVC and RA are driven by seasonal changes in circulating testosterone (T) levels. Infusing T, or its metabolites 5α‐dihydrotestosterone (DHT) and 17 β‐estradiol (E2), intracerebrally into HVC (but not RA) protects HVC neurons from death, and RA neuron size, in nonbreeding birds. The phosphoinositide 3‐kinase (PI3K)‐Akt (a serine/threonine kinase)‐mechanistic target of rapamycin (mTOR) signaling pathway is a point of convergence for neuroprotective effects of sex steroids and other trophic factors. We asked if mTOR activation is necessary for the protective effect of hormones in HVC and RA of adult male Gambel's white‐crowned sparrows (Zonotrichia leucophrys gambelii). We transferred sparrows from breeding to nonbreeding hormonal and photoperiod conditions to induce regression of HVC neurons by cell death and decrease of RA neuron size. We infused either DHT + E2, DHT + E2 plus the mTOR inhibitor rapamycin, or vehicle alone in HVC. Infusion of DHT + E2 protected both HVC and RA neurons. Coinfusion of rapamycin with DHT + E2, however, blocked the protective effect of hormones on HVC volume and neuron number, and RA neuron size. These results suggest that activation of mTOR is an essential downstream step in the neuroprotective cascade initiated by sex steroid hormones in the forebrain.

中文翻译：

---

雷帕霉素阻断成年鸟鸣系统中性类固醇的神经保护作用。

在成年鸣禽中，端脑鸣核HVC及其传出的目标RA的形态发生明显的季节性变化。与非繁殖鸟类相比，繁殖鸟类的HVC体积和总神经元数量以及RA神经元的体细胞面积都有所增加。繁殖结束时，HVC神经元通过caspase依赖性凋亡而死亡，因此RA神经元的大小减小。HVC和RA的变化是由循环睾丸激素（T）水平的季节性变化驱动的。将T或其代谢物5α-二氢睾丸激素（DHT）和17β-雌二醇（E2）大脑内注射到HVC中（而非RA）可保护HVC神经元免于死亡，并保护其在非繁殖禽类中的RA神经元大小。雷帕霉素（mTOR）信号通路的磷酸肌醇3激酶（PI3K）-Akt（丝氨酸/苏氨酸激酶）机制靶点是性类固醇和其他营养因子的神经保护作用的汇聚点。我们询问了mTOR活化对于成年雄性Gambel白冠麻雀的HVC和RA中激素的保护作用是否必要（Zonotrichia leucophrys gambelii）。我们将麻雀从繁殖期转移到非繁殖期的激素和光周期条件，以诱导HVC神经元因细胞死亡和RA神经元大小的减少而退化。我们将DHT + E2，DHT + E2加mTOR抑制剂雷帕霉素或单独的媒介物注入HVC中。输注DHT + E2可保护HVC和RA神经元。雷帕霉素与DHT + E2的共输注可阻断激素对HVC体积和神经元数量以及RA神经元大小的保护作用。这些结果表明，mTOR的激活是由前脑中的性类固醇激素引发的神经保护级联反应中必不可少的下游步骤。