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

被引：93

作者：

Bode, Felix J. ^{[2
]}

Stephan, Michael ^{[2
]}

Suhling, Hendrik ^{[2
]}

Pabst, Reinhard ^{[2
]}

Straub, Rainer H. ^{[3
]}

Raber, Kerstin A. ^{[1
]}

Bonin, Michael ^{[4
]}

Nguyen, Huu Phuc ^{[4
]}

Riess, Olaf ^{[4
]}

Bauer, Andreas ^{[5
,6
]}

Sjoberg, Charlotte ^{[7
]}

Petersen, Asa ^{[7
]}

von Hoersten, Stephan ^{[1
,2
]}

机构：

[1] Univ Erlangen Nurnberg, Franz Penzoldt Ctr, D-91054 Erlangen, Germany

[2] Hannover Med Sch, Inst Funct & Appl Anat, D-30625 Hannover, Germany

[3] Univ Regensburg, Dept Internal Med 1, D-93042 Regensburg, Germany

[4] Univ Tubingen, Dept Med Genet, D-72076 Tubingen, Germany

[5] Res Ctr Juelich, Inst Neurosci & Biophys, D-52425 Julich, Germany

[6] Univ Dusseldorf, Dept Neurol, D-40001 Dusseldorf, Germany

[7] Lund Univ, Translat Neuroendocrine Res Unit, Dept Expt Med Sci, S-22184 Lund, Sweden

来源：

HUMAN MOLECULAR GENETICS | 2008年 / 17卷 / 17期

关键词：

D O I：

10.1093/hmg/ddn159

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：2595 / 2609

页数：15

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