Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.
Brain Res. 2013 Jun 21;1516:76-82. doi: 10.1016/j.brainres.2013.04.002. Epub 2013 Apr 9.
A number of studies implicate neuroplasticity in the therapeutic mechanisms of antidepressants, specifically neuroplasticity in the dentate gyrus of the hippocampal formation. The dorsal hippocampal region in rodents is preferentially involved in spatial learning and memory, while the ventral hippocampal region plays a more important role in stress, emotion, and affective behaviors. These findings led us to investigate behavioral changes and gene expression changes in the ventral and dorsal dentate gyrus differentially after chronic treatment in mice with the antidepressant sertraline. Four-week treatment with sertraline significantly decreased immobility in the modified forced swim test, a behavioral test for assessing antidepressant-like effects in rodents. In the novelty-suppressed feeding test, performance of which is affected by functional changes in the dentate gyrus, sertraline treatment significantly decreased latency to feed. Next, we examined the expression of several neuroplasticity-related genes (those for Notch receptors, basic helix-loop-helix transcription factors and related factors, SoxC transcription factors, and glial-related genes) by real-time RT-PCR in the ventral and dorsal dentate gyrus of mice after the sertraline treatment. The gene encoding the neuropeptide galanin was significantly induced in only ventral dentate gyrus, not in dorsal dentate gyrus. These results suggest that sertraline-related galanin induction in ventral dentate gyrus may play an important role in therapeutic mechanisms for depression.
许多研究表明神经可塑性在抗抑郁药的治疗机制中起作用,特别是在海马结构的齿状回中的神经可塑性。啮齿动物的背侧海马区域优先参与空间学习和记忆,而腹侧海马区域在应激、情绪和情感行为中发挥更重要的作用。这些发现促使我们研究慢性给予抗抑郁药舍曲林后,在小鼠的腹侧和背侧齿状回中,行为变化和基因表达变化的差异。舍曲林治疗 4 周后,在改良强迫游泳试验中,即评估啮齿动物抗抑郁样效应的行为试验中,不动时间显著减少。在新颖性抑制进食试验中,齿状回的功能变化会影响其表现,舍曲林治疗后,进食潜伏期显著缩短。接下来,我们通过实时 RT-PCR 检查了几种神经可塑性相关基因(Notch 受体、碱性螺旋-环-螺旋转录因子和相关因子、SoxC 转录因子和神经胶质相关基因)在舍曲林治疗后小鼠的腹侧和背侧齿状回中的表达。只有在腹侧齿状回中,神经肽甘丙肽的编码基因显著诱导,而在背侧齿状回中则没有。这些结果表明,舍曲林相关的甘丙肽在腹侧齿状回中的诱导可能在抑郁症的治疗机制中起重要作用。