TY - JOUR T1 - Huntingtin Mediates Anxiety/Depression-Related Behaviors and Hippocampal Neurogenesis JF - The Journal of Neuroscience JO - J. Neurosci. SP - 8608 LP - 8620 DO - 10.1523/JNEUROSCI.5110-12.2013 VL - 33 IS - 20 AU - Karim Ben M'Barek AU - Patrick Pla AU - Sophie Orvoen AU - Caroline Benstaali AU - Juliette D. Godin AU - Alain M. Gardier AU - Frédéric Saudou AU - Denis J. David AU - Sandrine Humbert Y1 - 2013/05/15 UR - http://www.jneurosci.org/content/33/20/8608.abstract N2 - Huntington disease (HD) is associated with early psychiatric symptoms including anxiety and depression. Here, we demonstrate that wild-type huntingtin, the protein mutated in HD, modulates anxiety/depression-related behaviors according to its phosphorylation at serines 1181 and 1201. Genetic phospho-ablation at serines 1181 and 1201 in mouse reduces basal levels of anxiety/depression-like behaviors. We observe that the reduction in anxiety/depression-like phenotypes is associated with increased adult hippocampal neurogenesis. By improving the attachment of molecular motors to microtubules, huntingtin dephosphorylation increases axonal transport of BDNF, a crucial factor for hippocampal adult neurogenesis. Consequently, the huntingtin-mediated increased BDNF dynamics lead to an increased delivery and signaling of hippocampal BDNF. These results support the notion that huntingtin participates in anxiety and depression-like behavior and is thus relevant to the etiology of mood disorders and anxiety/depression in HD. ER -