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Sex differences in a transgenic rat model of Huntington's disease: decreased 17 beta-estradiol levels correlate with reduced numbers of DARPP32(+) neurons in males

Bode, Felix J.; Stephan, Michael; Suhling, Hendrik; Pabst, Reinhard; Straub, Rainer H.; Raber, Kerstin A.; Bonin, Michael; Nguyen, Huu Phuc; Riess, Olaf and Bauer, Andreas, et al. (2008) In Human Molecular Genetics 17(17). p.2595-2609
Abstract
Recent clinical studies have highlighted that female sex hormones represent potential neuroprotective mediators against damage caused by acute and chronic brain diseases. This evidence has been confirmed by experimental studies documenting the protective role of female sex hormones both in vitro and in vivo, although these studies did not specifically focus on Huntington's disease (HD). We therefore investigated the onset and course of HD in female and male transgenic (tg) HD (CAG(n51)) and control rats across age and focused on three aspects: (i) behavioral and physiological alterations (energy expenditure, home-cage activity, emotional disturbance and motor dysfunction), (ii) morphological markers (numbers and characteristics of striatal... (More)
Recent clinical studies have highlighted that female sex hormones represent potential neuroprotective mediators against damage caused by acute and chronic brain diseases. This evidence has been confirmed by experimental studies documenting the protective role of female sex hormones both in vitro and in vivo, although these studies did not specifically focus on Huntington's disease (HD). We therefore investigated the onset and course of HD in female and male transgenic (tg) HD (CAG(n51)) and control rats across age and focused on three aspects: (i) behavioral and physiological alterations (energy expenditure, home-cage activity, emotional disturbance and motor dysfunction), (ii) morphological markers (numbers and characteristics of striatal DARPP32(+) medium-sized spiny neurons (MSNs) and dopamine receptor autoradiography) and (iii) peripheral sex hormone levels as well as striatal estrogen receptor expression. Independent of their sex, tgHD rats exhibited increased levels of food intake, elevated home-cage activity scores and anxiolytic-like behavior, whereas only males showed an impairment of motor function. In line with the latter finding, loss and atrophy of DARPP32(+) MSNs were apparent only in male tgHD rats. This result was associated with a decreased striatal dopamine D1 receptor density and lower plasma levels of 17 beta-estradiol at the age of 14 months. As DARPP32(+) MSNs expressed both alpha-and beta-estrogen receptors and showed a correlation between cell numbers and 17 beta-estradiol levels, our findings suggest sex-related differences in the HD phenotype pointing to a substantial neuroprotective effect of sex hormones and opening new perspectives on the therapy of HD. (Less)
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Human Molecular Genetics
volume
17
issue
17
pages
2595 - 2609
publisher
Oxford University Press
external identifiers
  • wos:000258867000002
  • scopus:49649121318
ISSN
0964-6906
DOI
10.1093/hmg/ddn159
language
English
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yes
id
841d96a8-8ea5-4867-b314-5a319ab394ab (old id 1247787)
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2008-11-10 11:15:58
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2017-11-12 03:22:03
@article{841d96a8-8ea5-4867-b314-5a319ab394ab,
  abstract     = {Recent clinical studies have highlighted that female sex hormones represent potential neuroprotective mediators against damage caused by acute and chronic brain diseases. This evidence has been confirmed by experimental studies documenting the protective role of female sex hormones both in vitro and in vivo, although these studies did not specifically focus on Huntington's disease (HD). We therefore investigated the onset and course of HD in female and male transgenic (tg) HD (CAG(n51)) and control rats across age and focused on three aspects: (i) behavioral and physiological alterations (energy expenditure, home-cage activity, emotional disturbance and motor dysfunction), (ii) morphological markers (numbers and characteristics of striatal DARPP32(+) medium-sized spiny neurons (MSNs) and dopamine receptor autoradiography) and (iii) peripheral sex hormone levels as well as striatal estrogen receptor expression. Independent of their sex, tgHD rats exhibited increased levels of food intake, elevated home-cage activity scores and anxiolytic-like behavior, whereas only males showed an impairment of motor function. In line with the latter finding, loss and atrophy of DARPP32(+) MSNs were apparent only in male tgHD rats. This result was associated with a decreased striatal dopamine D1 receptor density and lower plasma levels of 17 beta-estradiol at the age of 14 months. As DARPP32(+) MSNs expressed both alpha-and beta-estrogen receptors and showed a correlation between cell numbers and 17 beta-estradiol levels, our findings suggest sex-related differences in the HD phenotype pointing to a substantial neuroprotective effect of sex hormones and opening new perspectives on the therapy of HD.},
  author       = {Bode, Felix J. and Stephan, Michael and Suhling, Hendrik and Pabst, Reinhard and Straub, Rainer H. and Raber, Kerstin A. and Bonin, Michael and Nguyen, Huu Phuc and Riess, Olaf and Bauer, Andreas and Sjöberg, Charlotte and Petersén, Åsa and von Hoersten, Stephan},
  issn         = {0964-6906},
  language     = {eng},
  number       = {17},
  pages        = {2595--2609},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {Sex differences in a transgenic rat model of Huntington's disease: decreased 17 beta-estradiol levels correlate with reduced numbers of DARPP32(+) neurons in males},
  url          = {http://dx.doi.org/10.1093/hmg/ddn159},
  volume       = {17},
  year         = {2008},
}