Chronic stress is a major risk factor for the development of depression. Brain-derived neurotrophic factor (BDNF) plays an important role in neural functions and exhibits antidepressant effects. However, studies on depression-related behavioral response to BDNF have mainly focused on the limbic system, whereas other regions of the brain still require further exploration. Here, we report that exposure to chronic unpredictable stress (CUS) can induce depression-associated behaviors in mice. CUS could decrease total Bdnf mRNA and protein levels in the dorsal raphe nucleus (DRN), which correlated with depression-related behaviors. A corresponding reduction in exon-specific Bdnf mRNA was observed in the DRN of CUS mice. Bdnf was highly expressed in 5- Hydroxytryptamine (5-HT) neurons from the DRN. Selective deletion of Bdnf in 5-HT neurons alone could not induce anhedonia and behavioral despair in male or female mice, as indicated by the unchanged female urine sniffing time and preference for sucrose/saccharin. However, it could increase the latency to food in female mice, but not in male mice as shown by novelty-suppressed food test. Nevertheless, enhanced stress-induced susceptibility is observed in these male mice as suggested by the decrease in female urine sniffing time, and for female mice by the reduced sucrose preference and increased immobility in forced swim test. Furtherly, total Bdnf mRNA levels in DRN were correlated with depression-related behaviors of female, but not male 5-HT neurons specific Bdnf knockout mice. Our results indicate that BDNF might act on 5-HT neurons to regulate depression-related behaviors and stress vulnerability in a sex-dependent manner.

中文翻译：

---

5-HT 神经元中的脑源性神经营养因子调节亚慢性不可预测压力引起的抑郁相关行为的易感性。

慢性压力是抑郁症发展的主要危险因素。脑源性神经营养因子 (BDNF) 在神经功能中起重要作用并具有抗抑郁作用。然而，对 BDNF 的抑郁相关行为反应的研究主要集中在边缘系统，而大脑的其他区域仍需要进一步探索。在这里，我们报告暴露于慢性不可预测的压力 (CUS) 会导致小鼠出现抑郁相关行为。CUS 可以降低中缝背核 (DRN) 中的总 Bdnf mRNA 和蛋白质水平，这与抑郁相关行为相关。在 CUS 小鼠的 DRN 中观察到外显子特异性 Bdnf mRNA 的相应减少。Bdnf 在来自 DRN 的 5-羟色胺 (5-HT) 神经元中高度表达。仅在 5-HT 神经元中选择性删除 Bdnf 不会引起雄性或雌性小鼠的快感缺乏和行为绝望，如雌性尿液嗅探时间不变和对蔗糖/糖精的偏好所示。然而，它可能会增加雌性小鼠的食物潜伏期，但不会增加雄性小鼠的食物延迟，如新奇抑制食物测试所示。然而，在这些雄性小鼠中观察到增强的压力诱导易感性，这表现为雌性尿液嗅探时间的减少，而雌性小鼠的蔗糖偏好降低和强迫游泳试验中的不动性增加表明了这一点。此外，DRN 中的总 Bdnf mRNA 水平与雌性抑郁相关行为相关，但与雄性 5-HT 神经元特异性 Bdnf 敲除小鼠无关。