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 behaviours through its phosphorylation at serines 1181 and 1201, two cyclin-dependent kinase 5 phosphorylation sites. Indeed, genetic phospho-ablation at serines 1181 and 1201 in mouse reduces basal levels of anxiety/depression-like behaviours in mouse. These behavioural effects directly depend on increased adult hippocampal neurogenesis. Indeed, focal dentate gyrus irradiation impaired neurogenesis but also anxiety/depression-related behaviour. Finally, the state of phosphorylation of huntingtin regulates neurogenesis as it influences brain-derived neurotrophic factor transport and subsequent signalling.
DD and SH are both equal last authors.
- BDNF transport
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.