Agomelatine, a new antidepressant, induces regional changes in hippocampal neurogenesis
Agomelatine, a new antidepressant, induces regional changes in hippocampal neurogenesis
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DOI：
10.1016/j.biopsych.2005.11.025
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发表时间：
2006-06-01
影响因子：
10.6
通讯作者：
Daszuta, Annie
中科院分区：
文献类型：
--
作者：
Banasr, Mounira;Soumier, Amelie;Daszuta, Annie
背景：抗抑郁治疗增加神经可塑性和成年神经发生，特别是在海马。在这里，我们确定阿戈美拉汀（S-20098），一种新的抗抑郁药，对成年大鼠齿状回神经发生的各个阶段的影响。方法：动物注射阿戈美拉汀不同的时间段。溴脱氧尿苷，神经元特异性核蛋白，神经胶质细胞酸性蛋白，以及高度聚唾液酸化形式的神经元细胞粘附分子和doublecortin的免疫染色，用于检测细胞增殖，神经发生和生存的变化。通过末端脱氧核苷酸转移酶介导的生物素化脱氧尿苷三磷酸缺口末端标记和甲酚紫染色来估计细胞死亡。阿戈美拉汀的慢性（3周）给药而非急性（4小时）或亚慢性（1周）给药增加了腹侧齿状回中的细胞增殖和神经发生，该区域特别涉及对情绪的反应，这与该药物的抗抑郁-抗焦虑特性一致。然而，将阿戈美拉汀治疗延长数周可增加整个齿状回中新形成的神经元的存活。最后，阿戈美拉汀治疗不影响成熟颗粒细胞。这项研究表明，抗抑郁药可以影响不同阶段的神经发生在背侧和腹侧海马。全部。这些变化导致新颗粒细胞总数的显著增加。
Background: Antidepressant treatments increase neural plasticity and adult neurogenesis, especially in the hippocampus. Here, we determined the effects of agomelatine (S-20098), a new antidepressant, on various phases of neurogenesis in the dentate gyrus of adult rat.Methods: Animals were injected with agomelatine for different time periods. Immunostaining for bromodeoxyuridine, neuron specific nuclear protein, and glial fibrillary acid protein, as well as for the highly polysialylated form of neuronal cell adhesion molecule and doublecortin, was used to detect changes in cell proliferation, neurogenesis, and survival. Cell death was estimated by terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end labeling and cresyl violet staining.Results: Chronic (3 weeks) but not acute (4 hours) or subchronic (1 week) administration of agomelatine increased cell proliferation and neurogenesis in the ventral dentate gyrus, a region notably implicated in response to emotion, which is consistent with the antidepressant-anxiolytic properties of the drug. Extending agomelatine treatment over several weeks, however, increases survival of new formed neurons in the entire dentate gyrus. Finally, agomelatine treatment does not affect mature granule cells.Conclusions. This study shows that an antidepressant can affect differentially various stages of neurogenesis in the dorsal and ventral hippocampus. Altogether. these changes lead to a pronounced augmentation in the total number of new granule cells.