Induction of galanin after chronic sertraline treatment in mouse ventral dentate gyrus
Induction of galanin after chronic sertraline treatment in mouse ventral dentate gyrus
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DOI：
10.1016/j.brainres.2013.04.002
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发表时间：
2013-06
期刊：
影响因子：
2.9
通讯作者：
M. Yamada;Y. Makino;Tomio Hashimoto;Azusa Sugiyama;J. Oka;M. Inagaki;M. Yamada;A. Saitoh
中科院分区：
文献类型：
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作者：
M. Yamada;Y. Makino;Tomio Hashimoto;Azusa Sugiyama;J. Oka;M. Inagaki;M. Yamada;A. Saitoh
许多研究表明，神经可塑性与抗抑郁药物的治疗机制有关，特别是在海马齿状回的神经可塑性。啮齿动物的背侧海马区优先参与空间学习和记忆，而腹侧海马区在应激、情绪和情感行为中发挥更重要的作用。这些发现导致我们研究了使用抗抑郁剂舍曲林慢性治疗后小鼠腹侧和背侧齿状回的行为变化和基因表达的变化。舍曲林四周的治疗显著减少了改进的强迫游泳试验中的不动，这是一种评估啮齿动物抗抑郁药样作用的行为测试。在新颖性抑制摄食测试中，舍曲林治疗显著缩短了进食潜伏期，其表现受到齿状回功能变化的影响。接下来，我们通过实时定量RT-PCR检测了舍曲林治疗后小鼠腹侧和背侧齿状回中几个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)的表达。编码神经肽甘丙肽的基因仅在腹侧齿状回被显著诱导，而在背侧齿状回中不被显著诱导。这些结果表明，舍曲林相关的甘丙素在腹侧齿状回的诱导可能在抑郁症的治疗机制中发挥重要作用。
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.