Several attempts have been made to understand the role of cholecalciferol (vitamin D₃) in the modulation of neuropsychiatric disorders. Notably, the deficiency of vitamin D₃ is considered a pandemic and has been postulated to enhance the risk of major depressive disorder (MDD). Therefore, this study aims to investigate the antidepressant-like effect of cholecalciferol in a mouse model of depression induced by corticosterone, and the possible role of glucocorticoid receptors (GR), NLRP3 and autophagic pathways in this effect. Corticosterone administration (20 mg/kg, p.o., for 21 days) significantly increased the immobility time and grooming latency, as well as reduced the total time spent grooming in mice subjected to the tail suspension test (TST) and splash test (ST), respectively. Importantly, these behavioral alterations were associated with reduced GR immunocontent in the hippocampus of mice. Conversely, the repeated administration of cholecalciferol (2.5 μg/kg, p.o.) in the last 7 days of corticosterone administration was effective to prevent the increased immobility time in the TST and the reduced time spent grooming in the ST, and partially abolished the increase in the grooming latency induced by corticosterone, suggesting its antidepressant-like effect. These behavioral effects were similar to those exerted by fluoxetine (10 mg/kg, p.o.). Moreover, the corticosterone-induced reduction on hippocampal GR immunocontent was not observed in mice treated with cholecalciferol. Additionally, cholecalciferol treatment per se reduced the immunocontent of NLRP3 inflammasome-related proteins ASC, caspase-1, and TXNIP in the hippocampus of mice. No alterations on hippocampal immunocontent of the autophagic-related proteins phospho-mTORC1, beclin-1, and LC3A/B were observed following cholecalciferol treatment and/or corticosterone administration. Collectively, our results provide insights into the effects of cholecalciferol in depression-related behaviors that seem to be related, at least in part, to GR modulation.

为了了解胆钙化固醇（维生素D ₃）在调节神经精神疾病中的作用，已经进行了几次尝试。值得注意的是，维生素D ₃缺乏被认为是大流行病，并被认为会增加患重度抑郁症（MDD）的风险。因此，本研究旨在探讨胆钙化固醇在皮质酮诱发的抑郁症小鼠模型中的抗抑郁样作用，以及糖皮质激素受体（GR），NLRP3和自噬途径在该作用中的可能作用。皮质酮（20 mg / kg，口服，持续21天）显着增加了固定时间和修饰潜伏期，并减少了在进行尾部悬吊试验（TST）和飞溅测试（ST）的小鼠中进行修饰的总时间，分别。重要的是，这些行为改变与小鼠海马中GR免疫含量降低有关。相反，重复给予胆钙化固醇（2.5μg/ kg，口服 ）在最后7天服用皮质类固醇可有效防止TST固定时间的增加和在ST中进行美容的时间减少，并部分消除了皮质类固醇诱导的美容潜伏时间的增加，表明其具有抗抑郁作用。这些行为影响类似于氟西汀（10 mg / kg，口服）。此外，在用胆钙化固醇治疗的小鼠中未观察到皮质酮诱导的海马GR免疫含量降低。此外，胆钙化醇治疗 这些行为影响类似于氟西汀（10 mg / kg，口服）。此外，在用胆钙化固醇治疗的小鼠中未观察到皮质酮诱导的海马GR免疫含量降低。此外，胆钙化醇治疗 这些行为影响类似于氟西汀（10 mg / kg，口服）。此外，在用胆钙化固醇治疗的小鼠中未观察到皮质酮诱导的海马GR免疫含量降低。此外，胆钙化醇治疗本身会降低小鼠海马中NLRP3炎性体相关蛋白ASC，caspase-1和TXNIP的免疫含量。胆钙化固醇治疗和/或皮质酮给药后，自噬相关蛋白磷酸-mTORC1，beclin-1和LC3A / B的海马免疫含量未见变化。总的来说，我们的研究结果提供了对胆钙化固醇在抑郁相关行为中的作用的洞察力，这些行为似乎至少部分与GR调节有关。