| First Author | Ben M'Barek K | Year | 2013 |
| Journal | J Neurosci | Volume | 33 |
| Issue | 20 | Pages | 8608-20 |
| PubMed ID | 23678106 | Mgi Jnum | J:198425 |
| Mgi Id | MGI:5496728 | Doi | 10.1523/JNEUROSCI.5110-12.2013 |
| Citation | Ben M'Barek K, et al. (2013) Huntingtin mediates anxiety/depression-related behaviors and hippocampal neurogenesis. J Neurosci 33(20):8608-20 |
| abstractText | 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. |
