PT  - JOURNAL ARTICLE
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
TI  - Huntingtin Mediates Anxiety/Depression-Related Behaviors and Hippocampal Neurogenesis
AID  - 10.1523/JNEUROSCI.5110-12.2013
DP  - 2013 May 15
TA  - The Journal of Neuroscience
PG  - 8608--8620
VI  - 33
IP  - 20
4099  - http://www.jneurosci.org/content/33/20/8608.short
4100  - http://www.jneurosci.org/content/33/20/8608.full
SO  - J. Neurosci.2013 May 15; 33
AB  - 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.