Elucidation of the pathogenic mechanisms underlying post-stroke depression (PSD) could aid in the development of effective treatments. The present study explored whether Vitamin D3 (VitD3) can function as an antidepressant in PSD model mice and whether the effect is mediated by upregulation of brain-derived neurotrophic factor (BDNF). Mice were subjected to middle cerebral artery occlusion (MCAO) combined with chronic unpredicted mild stress (CUMS) to established the PSD model. For the mice in each group, Longa and Berderson behavioral tests were performed to evaluate motor function, sucrose preference and forced swimming tests were conducted to assess the cardinal depression-like behaviors anhedonia and helplessness, and western blot and immunohistochemistry were conducted to measure the levels of vitamin D receptor (VDR) and BDNF expression levels in mouse hippocampus. Compared to MCAO alone, subsequent CUMS aggravated motor dysfunction and depression-like behaviors, whereas injection of calcitriol (VitD3) enhanced expression levels of VDR and BDNF in the hippocampus as well as ameliorated both motor dysfunction and depression-like behaviors of PSD model mice, with optimal efficacy at 25 μg/kg. Injection of a BDNF-binding protein (TrkB-IgG) almost completely reversed the antidepressant and neuroprotective effects of VitD3, strongly suggesting that VitD3 improved motor dysfunction and depression-like behaviors in PSD model mice by promoting hippocampal BDNF signaling. Modulation of hippocampal BDNF by VitD3 treatment could be an effective strategy for prevention and treatment of PSD.

阐明卒中后抑郁症 (PSD) 的致病机制有助于开发有效的治疗方法。本研究探讨了维生素 D3 (VitD3) 是否可以在 PSD 模型小鼠中发挥抗抑郁作用，以及该作用是否由脑源性神经营养因子 (BDNF) 的上调介导。小鼠大脑中动脉闭塞（MCAO）联合慢性意外轻度应激（CUMS）建立PSD模型。对每组小鼠进行Longa和Berderson行为测试以评估运动功能，进行蔗糖偏好和强迫游泳测试以评估主要抑郁样行为的快感缺乏和无助，并进行蛋白质印迹和免疫组织化学以测量小鼠海马中维生素D受体（VDR）和BDNF表达水平。与单独的 MCAO 相比，随后的 CUMS 加重了运动功能障碍和抑郁样行为，而骨化三醇 (VitD3) 的注射增强了海马 VDR 和 BDNF 的表达水平，并改善了 PSD 模型小鼠的运动功能障碍和抑郁样行为，在 25 μg/kg 时具有最佳疗效。注射 BDNF 结合蛋白 (TrkB-IgG) 几乎完全逆转了 VitD3 的抗抑郁和神经保护作用，强烈表明 VitD3 通过促进海马 BDNF 信号传导改善了 PSD 模型小鼠的运动功能障碍和抑郁样行为。