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Anxiogenic-like behavior conditioned by ß-catenin expression in hippocampal progenitor cells

AuthorsVidal, Rebeca CSIC ORCID; Pilar-Cuéllar, Fuencisla CSIC ORCID; Linge, Raquel CSIC; Martín, Alicia CSIC; Díaz, Álvaro CSIC ORCID; Castro, Elena CSIC ORCID; Pazos, Ángel CSIC ORCID; Valdizán, Elsa M. CSIC ORCID
Knockout mice
Issue Date2014
CitationNeuroscience 2014
AbstractIt is well known that Wnt signaling pathway plays an important role in mood disorders pathophysiology, and ß-catenin is a crucial component of this pathway. The regulatory effect of ß-catenin upon neuronal differentiation/proliferation is proposed to be contributing within the context of neurogenesis and neuroplasticity to these diseases. In addition, it has been suggested that antidepressants may, at least in part, exert their neurogenic effects in the subgranular zone of the hippocampus by increasing levels of ß-catenin (Mostany et al., 2008). To further understand the role of ß-catenin in depression/anxiety, we generated conditional mice lacking ß-catenin in progenitor cells of the subgranular zone (SGZ) of hippocampus. These mice express CreERT under the control of the astrocyte-specific glutamate transporter (GLAST) promoter inducible by tamoxifen administration. Hippocampal neurogenesis was evaluated by measuring the level of BrdU+ cells in SGZ. We also tested several depression and anxiety-related behavioral responses in a time-dependent way after one and two months following tamoxifen administration. Efficiency of inducible recombination was examinated in Rosa 26 Cre-reporter mice and a high number of cells expressing LacZ in the SGZ were found. After one month of tamoxifen administration, the results demonstrated a significant decrease of BrdU+ cells in SGZ of hippocampus (p<0.05). In addition, behavioral tests revealed, on the one hand, an anxiogenic-like phenotype in the NSF (novelty suppressed feeding) in KO mice, as evidenced by an increase in the latency of feeding (354,0 ± 42,0 in KO vs 203,1 ± 33,8 in wt mice; p<0.05). In the same line, the light/dark box test (LDB, also predictive of anxiety-like behavior) showed that the KO animals spend less time in the light than in the dark section compared with wt mice (ratio L/D: 0,14 ± 0,04 in KO vs 0,30 ± 0,04 in wt mice; p<0.01). In contrast, two months after tamoxifen administration no changes were observed in BrdU+ cells nor in anxiety related tests compared with wt mice. Together, these results indicate that decreased ß-catenin expression in progenitor cells of hippocampal DG leads to decreased neurogenesis and may account for the anxiogenic response observed in KO mice. Interestingly, behavioral response recovers after two months of tamoxifen administration, an effect parallel to the recovery of neurogenesis in SGZ. Additional studies are necessary to clarify these results.
DescriptionResumen del póster presentado al Meeting Neuroscience 2014, celebrado en Washington DC (US) del 15 al 19 de noviembre de 2014.
Appears in Collections:(IBBTEC) Comunicaciones congresos
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