Antidepressant-like effects of translocator protein (18 kDa) ligand ZBD-2 in mouse models of postpartum depression.
Antidepressant-like effects of translocator protein (18 kDa) ligand ZBD-2 in mouse models of postpartum depression.
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易位蛋白 (18 kDa) 配体 ZBD-2 在小鼠产后抑郁模型中的抗抑郁样作用
DOI：
10.1186/s13041-018-0355-x
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发表时间：
2018-03-05
期刊：
影响因子：
3.6
通讯作者：
Liu SB
中科院分区：
文献类型：
--
作者：
Li XB;Liu A;Yang L;Zhang K;Wu YM;Zhao MG;Liu SB
18 kDa转运蛋白(TSPO)主要定位于中枢和外周神经系统类固醇合成细胞的线粒体膜外膜。该蛋白质的主要功能之一是将底物胆固醇运输到线粒体，这是合成类固醇的先决条件。临床试验表明，TSPO配体在治疗一些神经疾病和精神疾病方面可能有价值。然而，有关TSPO在产后抑郁(PPD)中的作用的信息有限。本实验室合成了XBD173的TSPO配体ZBD-2。采用行为学实验、酶联免疫吸附试验和Western印迹等方法，评价滋补阳虚汤-2‘S对PPD的治疗作用，并探讨其可能的分子机制。PPD模型大鼠杏仁基底外侧核TSPO水平显著降低。治疗2周后，ZBD-2可缓解PPD动物模型中的抑郁样行为，并提高TSPO水平。其作用机制可能与调节下丘脑-垂体-肾上腺轴，促进5-羟色胺和脑源性神经营养因子的分泌，维持兴奋性和抑制性突触蛋白的正常表达有关。我们的结果直接证实了ZBD-2对PPD具有治疗作用，为抗PPD药物的开发提供了新的靶点。
The 18 kDa translocator protein (TSPO) is primarily localized in the outer mitochondrial membrane of steroid-synthesizing cells in the central and peripheral nervous systems. One of the protein’s main functions is transporting substrate cholesterol into the mitochondria in a prerequisite process for steroid synthesis. Clinical trials have indicated that TSPO ligands might be valuable in treating some neuropathies and psychopathies. However, limited information is known about the role of TSPO in postpartum depression (PPD). The TSPO ligand ZBD-2, a derivative of XBD173, was synthesized in our laboratory. Behavioral tests, enzyme linked immunosorbent assay, and Western blot were employed to evaluate ZBD-2’s efficacy against PPD and to elucidate the potential underlying molecular mechanism. The TSPO levels significantly decreased in the basolateral amygdala of PPD models. After treatment for 2 weeks, ZBD-2 alleviated depression-like behaviors and enhanced the TSPO level in a PPD animal model. The underlying mechanisms of ZBD-2 were related to regulate the hypothalamic-pituitary-adrenal axis, enhance 5-HT and BDNF secretion, and maintain the excitatory and inhibitory synaptic protein expression to normal levels. Our results directly confirm that ZBD-2 exerts a therapeutic effect on PPD, which provides a new target for anti-PPD drug development.
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影响因子：
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作者：
Gourley, Shannon L;Taylor, Jane R
通讯作者：
Taylor, Jane R
DOI：
10.1007/s00737-017-0716-y
发表时间：
2017-06
期刊：
Archives of women's mental health
影响因子：
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作者：
Ferguson EH;Di Florio A;Pearson B;Putnam KT;Girdler S;Rubinow DR;Meltzer-Brody S
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Meltzer-Brody S
影响因子：
6.2
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通讯作者：
Guilarte, Tomas R.
DOI：
10.1017/s1461145710000738
发表时间：
2011-04-01
影响因子：
4.8
作者：
Klein, Anders B.;Williamson, Rebecca;Aznar, Susana
通讯作者：
Aznar, Susana
DOI：
10.1016/s0960-0760(99)00056-4
发表时间：
1999-04-01
影响因子：
4.1
作者：
Culty, M;Li, H;Papadopoulos, V
通讯作者：
Papadopoulos, V