RT Journal Article
SR Electronic
T1 Huntingtin Mediates Anxiety/Depression-Related Behaviors and Hippocampal Neurogenesis
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 8608
OP 8620
DO 10.1523/JNEUROSCI.5110-12.2013
VO 33
IS 20
A1 Karim Ben M'Barek
A1 Patrick Pla
A1 Sophie Orvoen
A1 Caroline Benstaali
A1 Juliette D. Godin
A1 Alain M. Gardier
A1 Frédéric Saudou
A1 Denis J. David
A1 Sandrine Humbert
YR 2013
UL http://www.jneurosci.org/content/33/20/8608.abstract
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.