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  • Title: Ventral hippocampal molecular pathways and impaired neurogenesis associated with 5-HT₁A and 5-HT₁B receptors disruption in mice.
    Author: Xia L, Deloménie C, David I, Rainer Q, Marouard M, Delacroix H, David DJ, Gardier AM, Guilloux JP.
    Journal: Neurosci Lett; 2012 Jul 11; 521(1):20-5. PubMed ID: 22622174.
    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.
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