Cognitive disorders and neurogenesis deficits in Huntington's disease mice are rescued by fluoxetine


Autoria(s): Grote, H. E.; Bull, N. D.; Howard, M. L.; Van Dellen, A.; Blakemore, C.; Bartlett, P. F.; Hannan, A. J.
Contribuinte(s)

Barry J. Everitt

Christopher E. Henderson

Data(s)

01/01/2005

Resumo

Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeat encoding an extended polyglutamine tract in the huntingtin protein. Affected individuals display progressive motor, cognitive and psychiatric symptoms (including depression), leading to terminal decline. Given that transgenic HD mice have decreased hippocampal cell proliferation and that a deficit in neurogenesis has been postulated as an underlying cause of depression, we hypothesized that decreased hippocampal neurogenesis contributes to depressive symptoms and cognitive decline in HD. Fluoxetine, a serotonin-reuptake inhibitor commonly prescribed for the treatment of depression, is known to increase neurogenesis in the dentate gyrus of wild-type mouse hippocampus. Here we show that hippocampal-dependent cognitive and depressive-like behavioural symptoms occur in HD mice, and that the administration of fluoxetine produces a marked improvement in these deficits. Furthermore, fluoxetine was found to rescue deficits of neurogenesis and volume loss in the dentate gyrus of HD mice.

Identificador

http://espace.library.uq.edu.au/view/UQ:77411

Idioma(s)

eng

Publicador

Federattion of European Neuroscience Societies

Palavras-Chave #Neurosciences #Depression #Hippocampus #Neurodegenerative #Serotonin-reuptake Inhibitor #Chronic Antidepressant Treatment #Cell-proliferation #Spontaneous-alternation #Neurotrophic Factor #Transgenic Mice #Dentate Gyrus #Adult Hippocampus #Rat Hippocampus #Mouse Model #Brain #C1 #320702 Central Nervous System #730104 Nervous system and disorders
Tipo

Journal Article