Contribution of hippocampal BDNF/CREB signaling pathway and gut microbiota to emotional behavior impairment induced by chronic unpredictable mild stress during pregnancy in rats offspring.
Contribution of hippocampal BDNF/CREB signaling pathway and gut microbiota to emotional behavior impairment induced by chronic unpredictable mild stress during pregnancy in rats offspring.
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作者：
Zhao F;Wang K;Wen Y;Chen X;Liu H;Qi F;Fu Y;Zhu J;Guan S;Liu Z
许多研究表明，暴露于产前母体压力（PMS）与后代的各种精神病理学结果有关。越来越多的证据表明肠道中的细菌和大脑中的神经元（微生物-肠道-大脑轴）之间存在联系;然而，缺乏关于肠道微生物群参与调节产前应激后代海马中BDNF/CREB信号通路的机制的研究。采用慢性轻度不可预见性应激（unpredictable mild stress，CWS）对孕鼠进行应激处理，建立孕鼠产前应激模型。测量体重并记录行为学变化。采用蔗糖偏好试验（SPT）、旷场试验（OFT）和悬尾试验（STT）测定子代的情绪状态。通过对微生物16 S rRNA V3-V4区域进行测序来评估肠道微生物群，并进行细菌群落结构和多样性的交互分析。RT-PCR和Western blotting分别检测海马BDNF、TrkB和CREB mRNA和蛋白的表达。产前母亲应激可增加孕妇血浆皮质酮水平，减缓孕妇体重增长，并引起抑郁样行为（均P < 0.05）。在子代中，产前母体应激使血浆皮质酮水平升高（P < 0.05），并观察到情绪行为改变（抑郁样状态）（P < 0.05）。母鼠孕期应激后子代肠道菌群的物种丰度、多样性和组成发生变化（P < 0.05）。与对照组的后代相比，乳杆菌科的物种多度下降，而胞菌科的物种多度上升。海马结构改变，BDNF/CREB信号通路表达减少（P < 0.05）。产前母体应激导致子代高皮质酮状态和异常情绪行为，可能与肠道菌群组成改变导致子代海马BDNF/CREB信号异常有关。
Numerous studies have shown that exposure to prenatal maternal stress (PMS) is associated with various psychopathological outcomes of offspring. The accumulating evidence linking bacteria in the gut and neurons in the brain (the microbiota-gut-brain axis) has been aconsensus; however, there is a lack of research on the involvement mechanism of gut microbiota in the regulation of the BDNF/CREB signaling pathway in the hippocampus of prenatally stressed offspring. Pregnant rats were subjected to chronic unpredictable mild stress (CUMS) to establish the prenatal maternal stress model. The body weight was measured and the behavioral changes were recorded. Offspring were tested to determine emotional state using sucrose preference test (SPT), open-field test (OFT) and suspended tail test (STT). Gut microbiota was evaluated by sequencing the microbial 16S rRNA V3–V4 region, and the interactive analysis of bacterial community structure and diversity was carried out. The expression of hippocampal BDNF, TrkB and CREB mRNA and proteins were respectively measured using RT-PCR and Western blotting. Prenatal maternal stress increased maternal plasma corticosterone levels, slowed maternal weight gain and caused depression-like behaviors (all P < 0.05). In offspring, prenatal maternal stress increased plasma corticosterone levels (P < 0.05) and emotional behavior changes (depression-like state) were observed (P < 0.05). The species abundance, diversity and composition of the offspring’s gut microbiota changed after the maternal stress during pregnancy (P < 0.05). Compared with the control group’s offspring, the species abundance of Lactobacillaceae was dropped, while the abundance of the Muribaculaceae species abundance was risen. Concurrent, changes in the hippocampal structure of the offspring and decreases in expression of BDNF/CREB signaling were noted (P < 0.05). Prenatal maternal stress leads to high corticosterone status and abnormal emotion behavior of offspring, which may be associated with the abnormal BDNF/CREB signaling in hippocampus of offspring caused by the change of gut microbiota composition.
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影响因子：
6.6
作者：
Gelaye, Bizu;Sanchez, Sixto E.;Williams, Michelle A.
通讯作者：
Williams, Michelle A.
DOI：
10.1073/pnas.1002601107
发表时间：
2010-06-29
影响因子：
11.1
作者：
Dominguez-Bello, Maria G.;Costello, Elizabeth K.;Knight, Rob
通讯作者：
Knight, Rob
影响因子：
2.7
作者：
Chagas, Luana A.;Batista, Tatiane H.;Vilela, Fabiana C.
通讯作者：
Vilela, Fabiana C.
影响因子：
56.9
作者：
Duckworth, Renee A.;Belloni, Virginia;Anderson, Samantha R.
通讯作者：
Anderson, Samantha R.
影响因子：
4
作者：
Gass, Peter;Riva, Marco A.
通讯作者：
Riva, Marco A.