Elevated Thyroid Peroxidase Antibody Increases Risk of Post-partum Depression by Decreasing Prefrontal Cortex BDNF and 5-HT Levels in Mice.
Elevated Thyroid Peroxidase Antibody Increases Risk of Post-partum Depression by Decreasing Prefrontal Cortex BDNF and 5-HT Levels in Mice.
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甲状腺过氧化物酶抗体升高通过降低小鼠前额皮质 BDNF 和 5-HT 水平来增加产后抑郁症的风险
DOI：
10.3389/fncel.2016.00307
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发表时间：
2016
影响因子：
5.3
通讯作者：
Teng W
中科院分区：
文献类型：
--
作者：
Zhou Y;Wang X;Zhao Y;Liu A;Zhao T;Zhang Y;Shan Z;Teng W
产后抑郁症（post - postpartum depression， PPD）是一种常见的围产期精神疾病，严重影响母亲及其后代。一些临床研究发现PPD与甲状腺过氧化物酶抗体（TPOAbs）有关；然而，这种关系背后的机制尚不清楚。本研究采用编码mTPO全长cDNA的腺病毒（mTPO- ad）免疫雌性C57BL/6小鼠，建立分离的tpoab阳性小鼠模型。采用强迫游泳测验（FST）、蔗糖偏好测验（SPT）和产后悬尾测验（TST）对产妇抑郁样行为进行评估。采用酶联免疫吸附试验（ELISA）测定妊娠前后血清TPOAb滴度。采用超高效液相色谱-串联质谱法（UHPLC-MS /MS）检测脑源性神经营养因子（BDNF） mRNA和蛋白表达水平，ELISA法检测血清素（5-HT）水平，总甲状腺素（TT4）水平。与对照组相比，mTPO-Ad免疫小鼠表现出抑郁行为，在12 h时间点蔗糖偏好（SP）明显降低，FST和TST的静止时间更长，并伴有BDNF和5-HT的表达降低，但前额皮质TT4浓度没有变化。总之，这些发现表明，TPOAb升高可能增加随后PPD的风险，并降低前额皮质中BDNF和5-HT的浓度。
Post-partum depression (PPD) is a common mental disease in the perinatal period that profoundly affects mothers and their offspring. Some clinical studies have found that PPD is related to thyroid peroxidase antibodies (TPOAbs); however, the mechanism underlying this relationship is unclear. Female C57BL/6 mice immunized with adenovirus encoding the cDNA of the full-length mTPO (mTPO-Ad) were used to establish the isolated TPOAb-positive mouse model in the present study. Maternal depressive-like behaviors were assessed using the forced swimming test (FST), sucrose preference test (SPT), and tail suspension test (TST) post-partum. The serum TPOAb titer was measured by enzyme-linked immunosorbent assay (ELISA) before pregnancy and post-partum. Furthermore, in the prefrontal cortex, the mRNA and protein expression levels of brain-derived neurotrophic factor (BDNF) were measured, serotonin (5-HT) levels were measured by ultra-high-performance liquid chromatography–tandem mass-spectrometry (UHPLC–MS/MS), and total thyroxine (TT4) levels were determined by ELISA. Compared with the controls, the mice immunized with mTPO-Ad displayed depressive behaviors, with a significantly lower sucrose preference (SP) at the 12-h time point and a longer immobility time in the FST and TST, which were accompanied by a lower expression of BDNF and 5-HT but no change in the TT4 concentration in the prefrontal cortex. Together, these findings suggest that elevated TPOAb may increase the risk of subsequent PPD and decrease the concentration of BDNF and 5-HT in the prefrontal cortex.
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DOI：
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