Department of Experimental and Clinical Pharmacology, Medical University in Lublin, Jaczewskiego 8, PL 20-090 Lublin, Poland.
Pharmacol Rep. 2011;63(2):537-43. doi: 10.1016/s1734-1140(11)70520-5.
Preclinical data indicate the antidepressant activity of zinc and the involvement of the brain-derived neurotrophic factor (BDNF) in this mechanism. The present study investigates the effect of chronic (16 days) combined treatment with zinc (15 mg/kg zinc hydroaspartate) and imipramine (5 mg/kg) in chronic unpredictable stress (CUS) on the BDNF mRNA level in the rat brain. Moreover, serum zinc concentrations were also assessed. CUS induced a significant reduction in the BDNF mRNA level in the hippocampus by 21% but had no effect in the frontal cortex. Repeated treatment with zinc induced a significant increase in the BDNF mRNA level in the hippocampus in the unstressed animals by 12% and as in the chronically stressed animals by 14%, compared to the appropriate controls. Imipramine treatment did not affect this factor. However, combined treatment of zinc and imipramine induced a 12% elevation of the BDNF mRNA level in the stressed but not in the unstressed rats. CUS induced a 19% reduction in the serum zinc concentration, whereas combined treatment of zinc and imipramine reduced this concentration by 24% in the unstressed and increased it (by 20%) in the stressed animals. These results indicate that: 1) CUS induces a reduction in the BDNF gene expression with a concomitant diminution of serum zinc concentration and 2) the CUS-induced reduction in the BDNF gene expression is antagonized by chronic treatment with zinc.
临床前数据表明锌具有抗抑郁活性，并且脑源性神经营养因子（BDNF）参与了这种机制。本研究调查了慢性（16 天）联合使用锌（15mg/kg 锌天冬氨酸）和丙咪嗪（5mg/kg）治疗慢性不可预测应激（CUS）对大鼠大脑中 BDNF mRNA 水平的影响。此外，还评估了血清锌浓度。CUS 导致海马体中的 BDNF mRNA 水平降低了 21%，但对额皮质没有影响。重复使用锌处理可使未应激动物的海马体中的 BDNF mRNA 水平增加 12%，慢性应激动物的 BDNF mRNA 水平增加 14%，与适当的对照组相比。丙咪嗪处理对该因子没有影响。但是，锌和丙咪嗪联合治疗可使应激大鼠的 BDNF mRNA 水平升高 12%，而未应激大鼠的 BDNF mRNA 水平则没有升高。CUS 导致血清锌浓度降低 19%，而锌和丙咪嗪的联合治疗则使未应激动物的血清锌浓度降低 24%，使应激动物的血清锌浓度升高（增加 20%）。这些结果表明：1）CUS 诱导 BDNF 基因表达减少，同时伴随血清锌浓度降低；2）CUS 诱导的 BDNF 基因表达减少被慢性锌处理拮抗。
