Ventral hippocampal molecular pathways and impaired neurogenesis associated with 5-HT1A and 5-HT1B receptors disruption in mice

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-HT1A and 5-HT1B receptors (5-HT1A/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-HT1A/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-HT1A/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-HT1A/1B-/- mice showed a decreased survival, but not proliferation of newborn cells in our model. (C) 2012 Elsevier Ireland Ltd. All rights reserved.