Banasr Mounira, Soumier Amélie, Hery Micheline, Mocaër Elisabeth, Daszuta Annie
Cell Interactions, Neurodegeneration and Neuroplasticity Unit, Unité Mixte de Recherche 6186, Centre National de la Recherche Scientifique, Marseille, France.
Biol Psychiatry. 2006 Jun 1;59(11):1087-96. doi: 10.1016/j.biopsych.2005.11.025. Epub 2006 Feb 24.
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.
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.
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 newly formed neurons in the entire dentate gyrus. Finally, agomelatine treatment does not affect mature granule cells.
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.
抗抑郁治疗可增加神经可塑性及成年神经发生，尤其是在海马体中。在此，我们确定了新型抗抑郁药阿戈美拉汀（S - 20098）对成年大鼠齿状回神经发生各阶段的影响。
给动物注射阿戈美拉汀不同时间段。使用溴脱氧尿苷、神经元特异性核蛋白、胶质纤维酸性蛋白以及高度多唾液酸化形式的神经元细胞黏附分子和双皮质素的免疫染色来检测细胞增殖、神经发生和存活的变化。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。
阿戈美拉汀慢性（3周）而非急性（4小时）或亚慢性（1周）给药可增加腹侧齿状回的细胞增殖和神经发生，腹侧齿状回是一个与情绪反应密切相关的区域，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神经元的存活。最后，阿戈美拉汀治疗不影响成熟颗粒细胞。
本研究表明，一种抗抑郁药可对背侧和腹侧海马体神经发生的不同阶段产生不同影响。总之，这些变化导致新颗粒细胞总数显著增加。
