Yucel Atakan, Yucel Nermin, Ozkanlar Seckin, Polat Elif, Kara Adem, Ozcan Halil, Gulec Mustafa
Department of Psychiatry, Erzurum Regional Education and Research Hospital, Erzurum, Turkey.
Department of Child and Adolescent Psychiatry, Faculty of Medicine, Ataturk University, Erzurum, Turkey.
Acta Histochem. 2016 Apr;118(3):299-304. doi: 10.1016/j.acthis.2016.02.007. Epub 2016 Mar 9.
Agomelatine (AG) is an agonist of melatonin receptors and an antagonist of the 5-HT2C-receptor subtype. The chronobiotic properties of AG are of significant interest due to the disorganization of internal rhythms, which might play a role in the pathophysiology of depression. The present study was designed to assess the effects of the antidepressant-like activity of AG, a new antidepressant drug, on adult neurogenesis and apoptosis using stress-exposed rat brains. Over the period of 1 week, the rats were exposed to light stress twice a day for 1h. After a period of 1 week, the rats were given AG treatment at a dose of either 10mg/kg or 40mg/kg for 15 days. The animals were then scarified, and the obtained tissue sections were stained with immuno-histochemical anti-BrdU, Caspase-3, and Bcl-2 antibodies. Serum brain-derived neurotrophic factor (BDNF) concentrations were measured biochemically using a BDNF Elisa kit. Biochemical BDNF analysis revealed a high concentration of BDNF in the serum of the stress-exposed group, but the concentrations of BDNF were much lower those of the AG-treated groups. Immuno-histochemical analysis revealed that AG treatment decreased the BrdU-positive and Bcl-2-positive cell densities and increased the Caspase-3-positive cell density in the hippocampus of stress-induced rats as compared to those of the stress group. The results of the study demonstrated that AG treatment ameliorated the hippocampal apoptotic cells and increased hippocampal neurogenesis. These results also strengthen the possible relationship between depression and adult neurogenesis, which must be studied further.
阿戈美拉汀（AG）是褪黑素受体激动剂和5-HT2C受体亚型拮抗剂。由于内部节律紊乱，AG的生物钟调节特性备受关注，这种节律紊乱可能在抑郁症的病理生理学中起作用。本研究旨在使用应激暴露大鼠脑评估新型抗抑郁药AG的抗抑郁样活性对成年神经发生和细胞凋亡的影响。在1周的时间里，大鼠每天接受两次光照应激，每次1小时。1周后，大鼠接受10mg/kg或40mg/kg剂量的AG治疗，持续15天。然后处死动物，将获得的组织切片用免疫组织化学抗BrdU、Caspase-3和Bcl-2抗体染色。使用BDNF酶联免疫吸附测定试剂盒通过生化方法测量血清脑源性神经营养因子（BDNF）浓度。生化BDNF分析显示，应激暴露组血清中BDNF浓度较高，但AG治疗组的BDNF浓度远低于应激暴露组。免疫组织化学分析显示，与应激组相比，AG治疗降低了应激诱导大鼠海马中BrdU阳性和Bcl-2阳性细胞密度，并增加了Caspase-3阳性细胞密度。研究结果表明，AG治疗改善了海马凋亡细胞并增加了海马神经发生。这些结果也加强了抑郁症与成年神经发生之间可能存在的关系，这一点必须进一步研究。
