Psychiatric and metabolic disturbances in experimental models of Huntington’s disease
Author
Summary, in English
In this thesis, we showed that the BACHD mouse, a model engineered to allow conditional inactivation of mutant huntingtin expression, displays early psychiatric-like behaviors in addition to metabolic disturbances. The development of metabolic alterations could be prevented and depressive-like behavior reduced in young BACHD mice by selective inactivation of mutant huntingtin expression in the hypothalamus. In a second mouse model, viral vector-mediated expression of mutant huntingtin in the hypothalamus was sufficient to recapitulate the metabolic phenotype observed in the BACHD mice. Importantly, both studies revealed adverse effects on the hypothalamic orexin system. By contrast, inactivation of mutant huntingtin in leptin receptor-expressing neurons in the BACHD mice had no effect on the observed phenotypes, indicating that leptin is unlikely to be involved. Taken together, these results suggest a link between mutant huntingtin acting in the hypothalamus and the development of psychiatric and metabolic disturbances in HD.
Department/s
Publishing year
2014
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2014:67
Document type
Dissertation
Publisher
Department of Experimental Medical Science, Lund Univeristy
Topic
- Basic Medicine
Keywords
- Huntington’s disease
- huntingtin
- hypothalamus
- depression
- anxiety
- metabolism
- neuroendocrinology
- mouse models
- BACHD
- rAAV vectors
- leptin
Status
Published
Research group
- Translational Neuroendocrinology
Supervisor
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-87651-94-6
Defence date
28 May 2014
Defence time
13:00
Defence place
Segerfalksalen, BMC, Sölvegatan 17, Lund
Opponent
- Per Svenningsson (Professor)