Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis 88040-900, SC, Brazil.
Department of Natural Sciences, Center of Exact and Natural Sciences, Universidade Regional de Blumenau, CEP 89030-903 Blumenau, Santa Catarina, Brazil.
Pharmacol Biochem Behav. 2020 Sep;196:172971. doi: 10.1016/j.pbb.2020.172971. Epub 2020 Jun 23.
Several attempts have been made to understand the role of cholecalciferol (vitamin D) in the modulation of neuropsychiatric disorders. Notably, the deficiency of vitamin D 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.
已经有几项尝试旨在理解胆钙化醇（维生素 D）在神经精神疾病调节中的作用。值得注意的是，维生素 D 缺乏被认为是一种大流行，并被假设会增加重度抑郁症（MDD）的风险。因此，本研究旨在研究胆钙化醇在皮质酮诱导的抑郁小鼠模型中的抗抑郁样作用，以及糖皮质激素受体（GR）、NLRP3 和自噬途径在这种作用中的可能作用。皮质酮给药（20mg/kg，口服，共 21 天）显著增加了悬尾试验（TST）和浸水试验（ST）中小鼠的不动时间和梳理潜伏期，并分别减少了梳理总时间。重要的是，这些行为改变与小鼠海马中 GR 免疫含量的减少有关。相反，在皮质酮给药的最后 7 天重复给予胆钙化醇（2.5μg/kg，口服）可有效预防 TST 中不动时间的增加和 ST 中梳理时间的减少，并部分消除皮质酮引起的梳理潜伏期增加，表明其具有抗抑郁样作用。这些行为效应与氟西汀（10mg/kg，口服）产生的效应相似。此外，在给予胆钙化醇的小鼠中未观察到皮质酮诱导的海马 GR 免疫含量减少。此外，胆钙化醇本身的治疗降低了小鼠海马中 NLRP3 炎症小体相关蛋白 ASC、caspase-1 和 TXNIP 的免疫含量。在给予胆钙化醇和/或皮质酮后，未观察到海马中与自噬相关的蛋白磷酸-mTORC1、beclin-1 和 LC3A/B 的免疫含量改变。总之，我们的结果提供了关于胆钙化醇在与抑郁相关的行为中的作用的见解，这些作用至少部分与 GR 调节有关。
