Szopa Aleksandra, Herbet Mariola, Poleszak Ewa, Bogatko Karolina, Ostrowska-Leśko Marta, Świąder Katarzyna, Szponar Jarosław, Serefko Anna
Laboratory of Preclinical Testing, Chair and Department of Applied and Social Pharmacy, Medical University of Lublin, 1 Chodźki Street, 20-093 Lublin, Poland.
Chair and Department of Toxicology, Medical University of Lublin, 8 Chodźki Street, 20-093 Lublin, Poland.
Metabolites. 2022 Jun 23;12(7):586. doi: 10.3390/metabo12070586.
The main goal of this study was to determine the antidepressant-like potential of the co-administration of sodium selenite (Se) and the selective adenosine A1 and A2A antagonists DPCPX and istradefylline (IST), respectively, in mice despair tests. Biochemical studies were performed to elucidate the action mechanisms of the investigated treatment strategies. The results confirmed that, when administered by itself, Se exerts an antidepressant-like effect in the FST and TST and that this activity is dose-dependent. Further experiments demonstrated that Se (0.25 mg/kg) significantly enhanced the activity of mice in both tests when co-administered with DPCPX (1 mg/kg) and IST (0.5 mg/kg) at doses which would be ineffective if administered individually. Our research revealed that neither DPCPX, IST, nor Se or combinations of the tested substances induced significant changes in the brain-derived neurotrophic factor (BDNF) levels in mice serum vs. the NaCl-treated group. However, we observed a decrease in the mRNA level of antioxidant defense enzymes. Molecular studies also showed changes in the expression of the , , and genes, particularly after exposure to the combination of Se and DPCPX, which indicates a beneficial effect and may help to explain the key mechanism of the antidepressant effect. The combination of Se with substances attenuating adenosine neurotransmission may become a new therapeutic strategy for patients with depression.
本研究的主要目的是在小鼠绝望试验中分别确定亚硒酸钠（Se）与选择性腺苷A1和A2A拮抗剂二苯基环磷腺苷（DPCPX）及异丁司特（IST）联合给药的抗抑郁样潜力。进行了生化研究以阐明所研究治疗策略的作用机制。结果证实，单独给药时，Se在强迫游泳试验（FST）和悬尾试验（TST）中发挥抗抑郁样作用，且该活性具有剂量依赖性。进一步实验表明，当与DPCPX（1 mg/kg）和IST（0.5 mg/kg）联合给药时，Se（0.25 mg/kg）显著增强了小鼠在这两种试验中的活性，而单独给药时这两个剂量均无效。我们的研究表明，与氯化钠处理组相比，DPCPX、IST、Se或受试物质组合均未引起小鼠血清中脑源性神经营养因子（BDNF）水平的显著变化。然而，我们观察到抗氧化防御酶的mRNA水平有所下降。分子研究还显示了 、 和 基因表达的变化，特别是在暴露于Se和DPCPX的组合后，这表明有有益作用，并可能有助于解释抗抑郁作用的关键机制。Se与减弱腺苷神经传递的物质联合使用可能成为抑郁症患者的一种新治疗策略。
