Sex-specific neuroendocrine and behavioral phenotypes in hypomorphic Type II Neuregulin 1 rats.
Sex-specific neuroendocrine and behavioral phenotypes in hypomorphic Type II Neuregulin 1 rats.
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DOI：
10.1016/j.bbr.2011.05.008
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发表时间：
2011-10-31
影响因子：
2.7
通讯作者：
Koenig, James I.
中科院分区：
文献类型：
--
作者：
Taylor, Sara B.;Markham, Julie A.;Taylor, Adam R.;Kanaskie, Brooke Z.;Koenig, James I.
神经调节蛋白1（NRG 1）是一种重要的生长因子，参与中枢神经系统的发育和可塑性。自从NRG 1被鉴定为精神分裂症的易感基因以来，已经有几种转基因小鼠模型被用来阐明NRG 1在精神疾病发病机制中可能发挥的作用。不幸的是，很少有研究包括女性，尽管事实上，一些工作表明，破坏NRG 1表达的后果可能是性别特异性的。在这里，我们使用Nrg 1亚型（Nrg 1 Tn）菲舍尔大鼠表现出神经内分泌和行为表型的性别特异性变化的结果减少II型NRG 1的表达。我们以前已经表明，雄性Nrg 1 Tnrats增加了基础皮质酮水平，并未能习惯于一个开放的领域，尽管正常的整体水平的运动活动。目前的研究表明，相比之下，女性Nrg 1 Tnrats表现出增强的皮质酮水平的抑制急性应激后，减少运动活动，并增强适应新的环境。此外，我们还表明，女性，而不是男性，Nrg 1 Tnrats有受损的前脉冲抑制。最后，我们提供的证据表明，性别特异性的变化是不太可能归因于下丘脑-垂体-性腺轴的重大中断，作为措施的青春期开始，发情周期，和生殖能力在女性Nrg 1 Tnrats不变。我们的研究结果为NRG 1参与控制下丘脑-垂体-肾上腺轴功能和这种关系的性别特异性提供了进一步的支持。
Neuregulin 1 (NRG1) is an important growth factor involved in the development and plasticity of the central nervous system. Since its identification as a susceptibility gene for schizophrenia, several transgenic mouse models have been employed to elucidate the role NRG1 may play in the pathogenesis of psychiatric disease. Unfortunately very few studies have included females, despite the fact that some work suggests that the consequences of disrupted NRG1 expression may be sex-specific. Here, we used Nrg1 hypomorphic (Nrg1Tn) Fischer rats to demonstrate sex-specific changes in neuroendocrine and behavioral phenotypes as a consequence of reduced Type II NRG1 expression. We have previously shown that male Nrg1Tnrats have increased basal corticosterone levels, and fail to habituate to an open field despite normal overall levels of locomotor activity. The current studies show that, in contrast, female Nrg1Tnrats exhibit enhanced suppression of corticosterone levels following an acute stress, reduced locomotor activity, and enhanced habituation to novel environments. Furthermore, we also show that female, but not male, Nrg1Tnrats have impaired prepulse inhibition. Finally, we provide evidence that sex-specific changes are not likely attributable to major disruptions in the hypothalamic-pituitary-gonadal axis, as measures of pubertal onset, estrous cyclicity, and reproductive capacity were unaltered in female Nrg1Tnrats. Our results provide further support for both the involvement of NRG1 in the control of hypothalamic-pituitary-adrenal axis function and the sex-specific nature of this relationship.
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DOI：
10.1523/jneurosci.1815-08.2008
发表时间：
2008-07-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Chen YJ;Johnson MA;Lieberman MD;Goodchild RE;Schobel S;Lewandowski N;Rosoklija G;Liu RC;Gingrich JA;Small S;Moore H;Dwork AJ;Talmage DA;Role LW
通讯作者：
Role LW
影响因子：
3.7
作者：
Hinz, B;Hirschelmann, R
通讯作者：
Hirschelmann, R
DOI：
10.1111/j.1749-6632.1997.tb48289.x
发表时间：
1997-01-01
期刊：
PSYCHOBIOLOGY OF POSTTRAUMATIC STRESS DISORDER
影响因子：
--
作者：
Davis, M;Walker, DL;Lee, YL
通讯作者：
Lee, YL
影响因子：
2.5
作者：
Blurton-Jones, Mathew;Tuszynsk, Mark H.
通讯作者：
Tuszynsk, Mark H.
影响因子：
4.5
作者：
Dean, Brian;Karl, Tim;Scarr, Elizabeth
通讯作者：
Scarr, Elizabeth