Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy.
J Pineal Res. 2010 Sep;49(2):123-9. doi: 10.1111/j.1600-079X.2010.00775.x. Epub 2010 Jun 1.
Melatonin, involved in circadian cycle, provides protective effects on neuronal cells and acts as antidepressant by restoration of corticosterone levels. A mouse model of anxiety/depressive-like behavior, induced by chronic corticosterone treatment, has been used to evaluate behavior and adult hippocampal neurogenesis in mice and their possible modulation under melatonin. With this aim, CD1 mice were subjected to 7 wk of corticosterone administration, and then behavioral tests as novelty-suppressed feeding, open field and a forced swim test were performed. Cell proliferation in hippocampal dentate gyrus (DG) was investigated by 5-bromo-2'-deoxyuridine and doublecortin immunohistochemistry techniques, and stereological procedure was used to quantify labeled cells. Golgi-impregnated method was used to evaluate the changes of dendritic spines in DG neurons. A new therapeutic approach with antidepressant-like substances (3 wk) such as melatonin (8 mg/kg) was employed to possibly modulate neural development in the adult hippocampus and the behavioral changes. The depressive-like state caused by chronic corticosterone treatment was reversed by exogenous administration of melatonin; the proliferation of progenitor cells in mice hippocampus was significantly reduced under chronic corticosterone treatment (cort- 83.7 +/- 20.3 versus cort+ 60.5 +/- 18.2; P < 0.05), whereas long-term treatment with melatonin prevented the corticosterone-induced reduction in hippocampal cell proliferation (cort- 60.5 +/- 18.2 versus mel 133.4 +/- 26.9; P < 0.05). Corticosterone-treated mice exhibited a reduced spine density, which was ameliorated by melatonin administration. These findings suggest a strong correspondence between behavior and neurogenesis, strengthening the hypothesis that neurogenesis contributes to the effects of melatonin as an antidepressant.
褪黑素参与生物钟周期，通过恢复皮质酮水平对神经元细胞发挥保护作用，并具有抗抑郁作用。慢性皮质酮处理诱导的焦虑/抑郁样行为的小鼠模型已被用于评估小鼠的行为和成年海马神经发生及其在褪黑素下的可能调节。为此，将 CD1 小鼠用皮质酮处理 7 周，然后进行新奇抑制喂养、旷场和强迫游泳试验等行为测试。通过 5-溴-2'-脱氧尿苷和双皮质素免疫组织化学技术研究海马齿状回（DG）中的细胞增殖，并使用体视学程序定量标记细胞。用高尔基浸渍法评估 DG 神经元树突棘的变化。采用具有抗抑郁作用的物质（3 周），如褪黑素（8mg/kg）的新治疗方法，可能调节成年海马体中的神经发育和行为变化。慢性皮质酮处理引起的抑郁样状态被外源性褪黑素给药逆转；慢性皮质酮处理（皮质酮-83.7±20.3 与皮质酮+60.5±18.2；P<0.05）显著降低了小鼠海马祖细胞的增殖，而长期褪黑素治疗可预防皮质酮引起的海马细胞增殖减少（皮质酮-60.5±18.2 与褪黑素 133.4±26.9；P<0.05）。皮质酮处理的小鼠表现出树突棘密度降低，褪黑素给药可改善这种情况。这些发现表明行为和神经发生之间存在很强的对应关系，这加强了神经发生有助于褪黑素作为抗抑郁药的作用的假设。
