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Metabolic and behavioral effects of mutant huntingtin deletion in Sim1 neurons in the BACHD mouse model of Huntington's disease

Soylu-Kucharz, Rana LU ; Baldo, Barbara LU and Petersén, Åsa LU (2016) In Scientific Reports 6.
Abstract

Hypothalamic pathology, metabolic dysfunction and psychiatric symptoms are part of Huntington disease (HD), which is caused by an expanded CAG repeat in the huntingtin (HTT) gene. Inactivation of mutant HTT selectively in the hypothalamus prevents the development of metabolic dysfunction and depressive-like behavior in the BACHD mouse model. The hypothalamic paraventricular nucleus (PVN) is implicated in metabolic and emotional control, therefore we here tested whether inactivation of mutant HTT in the PVN affects metabolic and psychiatric manifestations of HD in BACHD mice. BACHD mice were crossed with mice expressing Cre-recombinase under the Sim1 promoter (Sim1-Cre) to inactivate mutant HTT in Sim1 expressing cells, i.e. the PVN of... (More)

Hypothalamic pathology, metabolic dysfunction and psychiatric symptoms are part of Huntington disease (HD), which is caused by an expanded CAG repeat in the huntingtin (HTT) gene. Inactivation of mutant HTT selectively in the hypothalamus prevents the development of metabolic dysfunction and depressive-like behavior in the BACHD mouse model. The hypothalamic paraventricular nucleus (PVN) is implicated in metabolic and emotional control, therefore we here tested whether inactivation of mutant HTT in the PVN affects metabolic and psychiatric manifestations of HD in BACHD mice. BACHD mice were crossed with mice expressing Cre-recombinase under the Sim1 promoter (Sim1-Cre) to inactivate mutant HTT in Sim1 expressing cells, i.e. the PVN of the hypothalamus. We found that inactivation of mutant HTT in Sim1 cells had a sex-specific effect on both the metabolic and the psychiatric phenotype, as these phenotypes were no longer different in male BACHD/Sim1-Cre mice compared to wild-type littermates. We also found a reduced number of GnRH neurons specifically in the anterior hypothalamus and an increased testes weight in male BACHD mice compared to wild-type littermates. Taken together, expression of mutant HTT in Sim1 cells may play a role for the development of metabolic dysfunction and depressive-like behavior in male BACHD mice.

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organization
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publication status
published
subject
in
Scientific Reports
volume
6
publisher
Nature Publishing Group
external identifiers
  • Scopus:84975780621
  • WOS:000378316400001
ISSN
2045-2322
DOI
10.1038/srep28322
language
English
LU publication?
yes
id
d11cb2bc-de9a-4aff-830b-47ddc0526942
date added to LUP
2016-07-26 12:04:45
date last changed
2017-01-01 08:31:13
@article{d11cb2bc-de9a-4aff-830b-47ddc0526942,
  abstract     = {<p>Hypothalamic pathology, metabolic dysfunction and psychiatric symptoms are part of Huntington disease (HD), which is caused by an expanded CAG repeat in the huntingtin (HTT) gene. Inactivation of mutant HTT selectively in the hypothalamus prevents the development of metabolic dysfunction and depressive-like behavior in the BACHD mouse model. The hypothalamic paraventricular nucleus (PVN) is implicated in metabolic and emotional control, therefore we here tested whether inactivation of mutant HTT in the PVN affects metabolic and psychiatric manifestations of HD in BACHD mice. BACHD mice were crossed with mice expressing Cre-recombinase under the Sim1 promoter (Sim1-Cre) to inactivate mutant HTT in Sim1 expressing cells, i.e. the PVN of the hypothalamus. We found that inactivation of mutant HTT in Sim1 cells had a sex-specific effect on both the metabolic and the psychiatric phenotype, as these phenotypes were no longer different in male BACHD/Sim1-Cre mice compared to wild-type littermates. We also found a reduced number of GnRH neurons specifically in the anterior hypothalamus and an increased testes weight in male BACHD mice compared to wild-type littermates. Taken together, expression of mutant HTT in Sim1 cells may play a role for the development of metabolic dysfunction and depressive-like behavior in male BACHD mice.</p>},
  articleno    = {28322},
  author       = {Soylu-Kucharz, Rana and Baldo, Barbara and Petersén, Åsa},
  issn         = {2045-2322},
  language     = {eng},
  month        = {06},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Metabolic and behavioral effects of mutant huntingtin deletion in Sim1 neurons in the BACHD mouse model of Huntington's disease},
  url          = {http://dx.doi.org/10.1038/srep28322},
  volume       = {6},
  year         = {2016},
}