Effects of peripubertal gonadotropin-releasing hormone agonist on brain development in sheep - A magnetic resonance imaging study [Psychoneuroendocrinology 38 (10) (2013) 1994-2002]

Effects of peripubertal gonadotropin-releasing hormone agonist on brain development in sheep - A magnetic resonance imaging study [Psychoneuroendocrinology 38 (10) (2013) 1994-2002]
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围青春期促性腺激素释放激素激动剂对绵羊大脑发育的影响 - 磁共振成像研究 [Psychoneuroendocrinology 38 (10) (2013) 1994-2002]

DOI:
10.1016/j.psyneuen.2013.10.016
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发表时间:
2014
影响因子:
3.7
通讯作者:
Nuruddin S
Nuruddin S
中科院分区:
医学2区
文献类型:
--
作者:
Nuruddin S

文献摘要

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在许多物种中,大脑结构和功能的两性异形已经被证明。在绵羊模型中,我们先前已经证明,围青春期药物阻断促性腺激素释放激素(GnRH)的作用增加了执行情绪行为的性别差异。然而,这种行为改变的结构基础是未知的。在这项对相同动物的磁共振成像(MRI)研究中,我们研究了GnRH激动剂(GnRHa)治疗对全脑、海马和杏仁核体积的影响,共41个脑(17个治疗组; 10个雌性和7个雄性; 24个对照组; 11个雌性和13个雄性)被纳入MRI研究。图像采集采用3-T MRI扫描仪。杏仁核和海马体的分割通过手动追踪完成,总灰质和白色物质体积通过对个体T2加权MRI体积的自动脑体积分割来估计。用一般线性模型进行统计学比较,发现GnRHa对左右杏仁核体积有高度显著的处理效应,表明处理动物的杏仁核较大。总灰质和右侧杏仁核存在显著的性别差异,表明雄性动物的体积大于雌性动物。此外,我们观察到性别和给药对左杏仁核体积的显著相互作用,表明给药对雌性动物的影响强于雄性动物。GnRHa治疗对杏仁核体积的影响表明,青春期GnRH浓度的增加可能对哺乳动物的正常大脑发育产生重要影响。这些新的发现证实了需要进一步研究GnRHa治疗对年轻动物和人类大脑的潜在神经生物学副作用。
In many species sexual dimorphisms in brain structures and functions have been documented. In ovine model, we have previously demonstrated that peri-pubertal pharmacological blockade of gonadotropin releasing hormone (GnRH) action increased sex-differences of executive emotional behavior. The structural substrate of this behavioral alteration however is unknown. In this magnetic resonance image (MRI) study on the same animals, we investigated the effects of GnRH agonist (GnRHa) treatment on the volume of total brain, hippocampus and amygdala.In total 41 brains (17 treated; 10 females and 7 males, and 24 controls; 11 females and 13 males) were included in the MRI study. Image acquisition was performed with 3-T MRI scanner. Segmentation of the amygdala and the hippocampus was done by manual tracing and total gray and white matter volumes were estimated by means of automated brain volume segmentation of the individual T2-weighted MRI volumes. Statistical comparisons were performed with general linear models.Highly significant GnRHa treatment effects were found on the volume of left and right amygdala, indicating larger amygdalae in treated animals. Significant sex differences were found for total gray matter and right amygdala, indicating larger volumes in male compared to female animals. Additionally, we observed a significant interaction between sex and treatment on left amygdala volume, indicating stronger effects of treatment in female compared to male animals. The effects of GnRHa treatment on amygdala volumes indicate that increasing GnRH concentration during puberty may have an important impact on normal brain development in mammals. These novel findings substantiate the need for further studies investigating potential neurobiological side effects of GnRHa treatment on the brains of young animals and humans.