Lucassen Paul J, Fuchs Eberhard, Czéh Boldizsár
Institute for Neurobiology, Faculty of Science, Swammerdam Institute for Life Sciences, University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam, The Netherlands.
Biol Psychiatry. 2004 Apr 15;55(8):789-96. doi: 10.1016/j.biopsych.2003.12.014.
Recent clinical and preclinical studies suggest that major depression may be related to impairments of structural plasticity. Consequently, antidepressants may act by restoring altered rates of cell birth or death. Here, we investigated whether the antidepressant tianeptine would affect apoptosis in an animal model of depression, the psychosocially stressed tree shrew.
Animals were subjected to a 7-day period of psychosocial stress before the onset of daily administration of tianeptine. Stress continued throughout the 28-day treatment period. In situ end labeling was used to detect apoptosis in hippocampus and adjacent temporal cortex.
Both stress and tianeptine treatment had a region-specific effect. Stress increased apoptosis in the temporal cortex, while it reduced it in the Ammons Horn. No significant effect was observed in the dentate gyrus. Interestingly, tianeptine treatment significantly reduced apoptosis in the temporal cortex and dentate gyrus, both in control and stressed animals, but had no effect in the Ammons Horn. Parallel Fluoro-Jade staining indicated that this apoptosis most likely represents non-neuronal cells.
This is the first report showing an anti-apoptotic effect of tianeptine in hippocampal subfields and temporal cortex. These findings are consistent with current theories that ascribe enhanced general cell survival to antidepressant action.
近期的临床和临床前研究表明，重度抑郁症可能与结构可塑性受损有关。因此，抗抑郁药可能通过恢复细胞生成或死亡的改变速率来发挥作用。在此，我们研究了抗抑郁药噻奈普汀是否会影响抑郁症动物模型——遭受心理社会应激的树鼩的细胞凋亡。
在开始每日给予噻奈普汀之前对动物进行为期7天的心理社会应激。应激在整个28天的治疗期内持续存在。采用原位末端标记法检测海马体和相邻颞叶皮质中的细胞凋亡情况。
应激和噻奈普汀治疗均有区域特异性效应。应激增加了颞叶皮质中的细胞凋亡，但减少了海马角中的细胞凋亡。在齿状回中未观察到显著影响。有趣的是，噻奈普汀治疗显著降低了对照组和应激组动物颞叶皮质和齿状回中的细胞凋亡，但对海马角没有影响。平行的氟玉髓染色表明这种细胞凋亡很可能代表非神经元细胞。
这是首次报道噻奈普汀在海马亚区和颞叶皮质具有抗细胞凋亡作用。这些发现与当前将抗抑郁作用归因于增强一般细胞存活能力 的理论一致。
