期刊
NEUROSCIENCE LETTERS
卷 507, 期 2, 页码 127-132出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2011.11.063
关键词
Huntington's disease; Anxio-depressive-like behaviour; Neurogenesis; Hippocampus; Hdh(Q111) mice
资金
- French Ministry of Research
- University Paris-Sud
- CNRS
- INSERM
- Institut Curie
- Agence Nationale pour la Recherche [ANR-08-MNP-039]
- Association pour la Recherche sur le Cancer (ARC) [4950]
- Fondation pour la Recherche Medicale
- BQR from University Paris-Sud
Huntington's disease (HD) is a devastating genetic neurodegenerative disorder. Major depressive disorder and more generally mood disorders are a major component of the symptoms during the pre-motor symptomatic stages of the disease. We report here that knock-in Hdh(Q111) mice, an animal model of HD, that carry an expanded polyglutamine stretch in the mouse HD protein show an anxio-depressive-like phenotype prior to any impairment of the locomotor function. Strikingly, whereas females develop preferentially a depressive-like behaviour, males had an increased anxiety-like phenotype. Since adult hippocampal neurogenesis has been associated to the pathophysiology and treatment of depression, we investigated whether changes in behavioural phenotypes are associated with proliferation or maturation impairments. Whereas cell proliferation was not affected in knock-in Hdh(Q111) mice, a male-specific marked decrease in late maturation of newborn neurons was observed in the adult dentate gyrus. Together, our results highlight sex differences in both behaviour and adult neurogenesis in a knock-in model of HD. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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