Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai, China.
Institute of Translational Research, Tongji Hospital, School of Life Sciences and Technology, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, Tongji University, Shanghai, China.
FASEB J. 2020 Oct;34(10):13257-13271. doi: 10.1096/fj.202000534R. Epub 2020 Aug 29.
Fetal growth restriction (FGR) is a severe perinatal complication that can increase risk for mental illness. To investigate the mechanism by which FGR mice develop mental illness in adulthood, we established the FGR mouse model and the FGR mice did not display obvious depression-like behaviors, but after environmental stress exposure, FGR mice were more likely to exhibit depression-like behaviors than control mice. Moreover, FGR mice had significantly fewer dopaminergic neurons in the ventral tegmental area but no difference in serotoninergic neurons in the dorsal raphe. RNA-seq analysis showed that the downregulated genes in the midbrain of FGR mice were associated with many mental diseases and were especially involved in the regulation of NMDA-selective glutamate receptor (NMDAR) activity. Furthermore, the NMDAR antagonist memantine can relieve the stress-induced depression-like behaviors of FGR mice. In summary, our findings provide a theoretical basis for future research and treatment of FGR-related depression.
胎儿生长受限（FGR）是一种严重的围产期并发症，可增加患精神疾病的风险。为了研究 FGR 小鼠在成年期患精神疾病的机制，我们建立了 FGR 小鼠模型，发现 FGR 小鼠并没有表现出明显的抑郁样行为，但在环境应激暴露后，FGR 小鼠比对照组小鼠更容易出现抑郁样行为。此外，FGR 小鼠腹侧被盖区的多巴胺能神经元明显减少，但中缝背核的 5-羟色胺能神经元没有差异。RNA-seq 分析表明，FGR 小鼠中脑下调的基因与许多精神疾病相关，尤其涉及 NMDA 选择性谷氨酸受体（NMDAR）活性的调节。此外，NMDAR 拮抗剂美金刚可以缓解 FGR 小鼠应激诱导的抑郁样行为。综上所述，我们的研究结果为未来 FGR 相关抑郁的研究和治疗提供了理论依据。
