Huntingtin Mediates Anxiety/Depression-Related Behaviors and Hippocampal Neurogenesis

• DOI: 10.1523/jneurosci.5110-12.2013
• Publication Date: 2013-05-15T17:05:06Z
• Authors: Karim Ben M'Barek; Patrick Pla; Sophie Orvoen; Caroline Benstaali; Juliette D. Godin; Alain M. Gardier; Frédéric Saudou; Denis J. David; Sandrine Humbert
• Keywords: Doublecortin Domain Proteins; Analysis of Variance; Huntingtin Protein; 0303 health sciences; Depression; [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology; Brain-Derived Neurotrophic Factor; Neurogenesis; Neuropeptides; Nuclear Proteins; Mice, Transgenic; Nerve Tissue Proteins; Anxiety; Hippocampus; Mice, Inbred C57BL; Disease Models, Animal; Mice; 03 medical and health sciences; Bromodeoxyuridine; In Situ Nick-End Labeling; Animals; Immunoprecipitation; Microtubule-Associated Proteins

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 1201. Genetic phospho-ablation 1201 mouse reduces basal levels of anxiety/depression-like behaviors. We observe reduction phenotypes increased adult hippocampal neurogenesis. By improving attachment molecular motors microtubules, huntingtin dephosphorylation increases axonal transport BDNF, a crucial factor for Consequently, huntingtin-mediated BDNF dynamics lead an delivery signaling BDNF. These results support notion participates depression-like behavior thus relevant etiology mood disorders anxiety/depression HD.