B14 Huntingtin mediates anxiety/depression-related behaviours in mouse through BDNF transport and hippocampal neurogenesis. (29th August 2012)

• Record Type: Journal Article
• Authors: Ben M'Barek, K; Orvoen, S; Pla, P; Benstaali, C; Godin, J; Gardier, A; Saudou, F; David, D; Humbert, S
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 83(2012)Supplement 1
• Page Start: A10
• Page End: A10
• Publication Date: 2012-08-29
• Subjects: Neurogenesis -- BDNF transport -- anxiety/depression -- hippocampus; Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2012-303524.30
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : 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.