Ventral hippocampal molecular pathways and impaired neurogenesis associated with 5-HT_1A and 5-HT_1B receptors disruption in mice

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• 作者：Lin Xia ; Claudine Delom¨¦nie ; Indira David ; Quentin Rainer ; Myriam Marouard ; Herv¨¦ Delacroix ; Denis J. David ; Alain M. Gardier ; Jean-Philippe Guilloux
• 关键词：Serotonin ; 5-HT1A and 5-HT1B receptors ; Hippocampus ; Microarray ; Neurogenesis
• 刊名：Neuroscience Letters
• 出版年：2012
• 出版时间：11 July, 2012
• 年：2012
• 卷：521
• 期：1
• 页码：20-25
• 全文大小：477 K

文摘

The serotonergic system has been widely implicated in stress related psychiatric disorders such as depression and anxiety. Generation of receptor knockout mice has offered a new approach to study processes underlying anxiety. For instance, knockout mice for both 5-HT_1A and 5-HT_1B receptors (5-HT_1A/1B^?/?) display an anxious phenotype, associated with robust physiological and neurochemical changes related to brain serotonin function. As ventral hippocampus is a key region in the mediation and genesis of anxiety, we explored the transcriptome changes induced by the genetic inactivation of these two receptors in 5-HT_1A/1B^?/? mice. Dissociation of ventral vs. dorsal hippocampus was confirmed by the over-expression of selective markers in both regions. 723 genes were observed up/down regulated in 5-HT_1A/1B^?/? mice. Using Ingenuity, biological networks and signal transduction pathway analysis corresponding to the identified gene revealed putative dysregulation of nervous system development and function, especially genes associated with long-term potentiation and adult neurogenesis (including Bdnf, Camk2a, Camk4, and Klf9). Furthermore, immunohistochemistry experiments studying adult hippocampal neurogenesis in adult 5-HT_1A/1B^?/? mice showed a decreased survival, but not proliferation of newborn cells in our model.