期刊
JOURNAL OF NEUROSCIENCE
卷 33, 期 20, 页码 8608-8620出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.5110-12.2013
关键词
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资金
- Agence Nationale pour la Recherche, Maladies Rares [ANR-09-BLAN-0080]
- Association pour la Recherche sur le Cancer (ARC) [3188]
- Federation pour la Recherche sur le Cerveau (FRC)
- CNRS
- INSERM
- Institut Curie
- Fondation pour la Recherche Medicale
- French Minister of Research
- Agence Nationale de la Recherche (ANR) [ANR-09-BLAN-0080] Funding Source: Agence Nationale de la Recherche (ANR)
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.
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