Continuous expression of corticotropin-releasing factor in the central nucleus of the amygdala emulates the dysregulation of the stress and reproductive axes.

Continuous expression of corticotropin-releasing factor in the central nucleus of the amygdala emulates the dysregulation of the stress and reproductive axes.
复制标题

DOI:
10.1038/mp.2008.91
复制
发表时间:
2009-01
影响因子:
11
通讯作者:
--
中科院分区:
医学1区
文献类型:
--
作者:

文献摘要

参考文献

被引文献

相似文献

促肾上腺皮质激素释放因子(CRF)的增加是应激相关疾病的病理生理学中的假定因素。由于杏仁核中央核(CeA)中CRF的表达在适应慢性应激中非常重要,我们假设CeA中CRF的无限制合成将模拟慢性应激暴露的后果,并引起下丘脑-垂体-肾上腺(HPA)轴的失调,增加情绪性并破坏生殖。为了验证这一假设,我们使用了慢病毒载体,以增加CRF的表达位点,特别是在CeA的雌性大鼠。增加合成的CRF在CeA放大CRF和精氨酸加压素肽浓度在下丘脑室旁核,并减少糖皮质激素的负反馈,这两个标志物与抑郁症的病理生理学。此外,持续表达CRF的CeA也增加了强迫游泳实验中的声惊吓反应和抑郁样行为。在视前内侧区的促性腺激素释放激素的蛋白水平显着降低CRF在CeA的连续表达,这是与发情周期延长。最后,性动机,但不是性接受性显着衰减连续CRF合成卵巢切除雌二醇-孕酮引发的女性。这些数据表明,不受限制的CRF合成在CeA产生HPA轴的失调,以及许多行为,生理和生殖的后果与压力相关的疾病。
An increase in corticotropin-releasing factor (CRF) is a putative factor in the pathophysiology of stress-related disorders. As CRF expression in the central nucleus of the amygdala (CeA) is important in adaptation to chronic stress, we hypothesized that unrestrained synthesis of CRF in CeA would mimic the consequences of chronic stress exposure and cause dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, increase emotionality and disrupt reproduction. To test this hypothesis, we used a lentiviral vector to increase CRF-expression site specifically in CeA of female rats. Increased synthesis of CRF in CeA amplified CRF and arginine vasopressin peptide concentration in the paraventricular nucleus of the hypothalamus, and decreased glucocorticoid negative feedback, both markers associated with the pathophysiology of depression. In addition, continuous expression of CRF in CeA also increased the acoustic startle response and depressive-like behavior in the forced swim test. Protein levels of gonadotropin-releasing hormone in the medial preoptic area were significantly reduced by continuous expression of CRF in CeA and this was associated with a lengthening of estrous cycles. Finally, sexual motivation but not sexual receptivity was significantly attenuated by continuous CRF synthesis in ovariectomized estradiol-progesterone-primed females. These data indicate that unrestrained CRF synthesis in CeA produces a dysregulation of the HPA axis, as well as many of the behavioral, physiological and reproductive consequences associated with stress-related disorders.
DOI: 10.1016/s0006-3223(01)01328-2
发表时间: 2002-01-01
影响因子: 10.6
作者:
Davidson, RJ
通讯作者: Davidson, RJ
DOI: 10.1152/ajpregu.1998.275.5.r1438
发表时间: 1998-11-01
影响因子: 2.8
作者:
Bonaz, B;Rivest, S
通讯作者: Rivest, S
DOI: 10.1089/hum.2005.16.741
发表时间: 2005-06-01
期刊: HUMAN GENE THERAPY
影响因子: 4.2
作者:
Abordo-Adesida, E;Follenzi, A;Lowenstein, PR
通讯作者: Lowenstein, PR
DOI: 10.1111/j.1365-2826.2007.01566.x
发表时间: 2007-08-01
影响因子: 3.2
作者:
Centeno, M.-L.;Sanchez, R. L.;Bethea, C. L.
通讯作者: Bethea, C. L.
DOI: 10.1080/10253890701391192
发表时间: 2007-01-01
影响因子: 2.3
作者:
Aguilera, Greti;Kiss, Alexander;Kamitakahara, Anna
通讯作者: Kamitakahara, Anna