ITMO University, Saint-Petersburg, Russia.
BMC Med Genet. 2019 Apr 9;20(Suppl 1):49. doi: 10.1186/s12881-019-0774-2.
Estrogen deficiency effects on affective-related behavior are restricted to certain periods of age after ovary removal. Among other nutraceuticals, one of such «natural» substances for treatment of affective-related diseases could be vitamin D. It is a great interest to evaluate the effects of repeated cholecalciferol administration on anxiety-related behavior in the old female rats with long-term estrogen deficiency. The present study was performed to determine the behavioral effects of cholecalciferol treatment at different doses as an adjunctive therapy alone or in a combination with low dose of 17β-estradiol on anxiety-like behavior of the old (16-18 months) female rats at 12 weeks after ovariectomy.
Vitamin D supplementation individually (as cholecalciferol at doses of 1.0, 2.5 or 5.0 mg/kg/day, s.c.) or in co-administration with of 17β-estradiol (17β-E, 0.5 μg/rat, s.c.) were given to the old ovariectomized (OVX) rats at 12 weeks after ovariectomy. Anxiety-related state was tested in the elevated plus maze (EPM) and light-dark test (LDT), as well behavioral reactivity was registered in the open field test (OFT). Moreover, 25-hydroxyvitamin D levels in the blood serum of these OVX rats treated with Vitamin D or Vitamin D plus 17β-E were measured.
The results of the present study indicated that Vitamin D supplementation at dose of 1.0 mg/kg/day decreased manifestations of anxiety-like profile in the old OVX rats. Treatment with Vitamin D (1.0 mg/kg/day) plus 17β-E in resulted in more profound anxiolytic-like effects the old OVX rats than effects of both drugs administered alone. Moreover, treatment with cholecalciferol (1.0 mg/kg/day, s.c.) in the old ovariectomized rats after ovariectomy at 12 weeks produced elevated estradiol and 25-OH-VD levels for these rats as compared to the old OVX females treated with oil solvent.
Using the preclinical study, chronic cholecalciferol, 17β-E and their combination treatment were shown to be effective for anxiety-like treatment in the old subjects with long-term estrogen deficiency.
雌激素缺乏对情感相关行为的影响仅限于卵巢切除后特定的年龄阶段。在其他营养药物中，维生素 D 可能是治疗情感相关疾病的一种“天然”物质。评估反复给予胆钙化醇对长期雌激素缺乏的老年雌性大鼠焦虑相关行为的影响具有重要意义。本研究旨在确定胆钙化醇治疗的行为影响，不同剂量的胆钙化醇单独或与低剂量 17β-雌二醇联合作为辅助治疗，对 12 周卵巢切除后老年（16-18 个月）雌性大鼠的焦虑样行为的影响。
维生素 D 补充剂（单独给予胆钙化醇，剂量为 1.0、2.5 或 5.0mg/kg/天，皮下注射）或与 17β-雌二醇（17β-E，0.5μg/大鼠，皮下注射）联合给予 12 周卵巢切除后的老年去卵巢（OVX）大鼠。在高架十字迷宫（EPM）和明暗试验（LDT）中测试焦虑相关状态，并在开阔场试验（OFT）中记录行为反应。此外，测量这些用维生素 D 或维生素 D 加 17β-E 治疗的 OVX 大鼠血清中 25-羟维生素 D 水平。
本研究结果表明，1.0mg/kg/天的胆钙化醇补充剂可降低老年 OVX 大鼠焦虑样表型的表现。与两种药物单独给药相比，17β-E 联合维生素 D（1.0mg/kg/天）治疗导致老年 OVX 大鼠产生更明显的抗焦虑样作用。此外，与用油溶剂治疗的老年 OVX 雌性大鼠相比，12 周卵巢切除后，1.0mg/kg/天的胆钙化醇（皮下注射）治疗可使老年去卵巢大鼠的雌二醇和 25-OH-VD 水平升高。
使用临床前研究，慢性胆钙化醇、17β-E 及其联合治疗对长期雌激素缺乏的老年患者的焦虑样治疗有效。
