title: Ventral hippocampal molecular pathways and impaired neurogenesis associated with 5-HT₁A and 5-HT₁B receptors disruption in mice.
abstract: 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.
authors.affiliation: Univ Paris-Sud, EA3544, Faculté de Pharmacie, Châtenay-Malabry F-92296, France.
authors.forename: Lin
authors.initials: L
authors.lastname: Xia
authors.forename: Claudine
authors.initials: C
authors.lastname: Deloménie
authors.forename: Indira
authors.initials: I
authors.lastname: David
authors.forename: Quentin
authors.initials: Q
authors.lastname: Rainer
authors.forename: Myriam
authors.initials: M
authors.lastname: Marouard
authors.forename: Hervé
authors.initials: H
authors.lastname: Delacroix
authors.forename: Denis J
authors.initials: DJ
authors.lastname: David
authors.forename: Alain M
authors.initials: AM
authors.lastname: Gardier
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Guilloux
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000502:physiology*; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics / Q000502:physiology*
chemical_list: D044302:Receptor, Serotonin, 5-HT1B; D044282:Receptor, Serotonin, 5-HT1A