Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, K7L 3N6, Canada.
Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, M5T 3H7, Canada.
Sci Rep. 2019 Jun 26;9(1):9285. doi: 10.1038/s41598-019-45824-6.
Offspring of preeclamptic pregnancies have cognitive alterations. Placental growth factor (PGF), is low in preeclampsia; reduced levels may affect brain development. PGF-null mice differ from normal congenic controls in cerebrovasculature, neuroanatomy and behavior. Using brain imaging and behavioral testing, we asked whether developmentally asynchronous (i.e. neonatal) PGF supplementation alters the vascular, neuroanatomic and/or behavioral status of Pgf mice at adulthood. C57BL/6-Pgf pups were treated intraperitoneally on postnatal days 1-10 with vehicle or PGF at 10 pg/g, 70 pg/g or 700 pg/g. These mice underwent behavioral testing and perfusion for MRI and analysis of retinal vasculature. A second cohort of vehicle- or PGF-treated mice was perfused for micro-CT imaging. 10 pg/g PGF-treated mice exhibited less locomotor activity and greater anxiety-like behavior relative to vehicle-treated mice. Depressive-like behavior showed a sex-specific, dose-dependent decrease and was lowest in 700 pg/g PGF-treated females relative to vehicle-treated females. Spatial learning did not differ. MRI revealed smaller volume of three structures in the 10 pg/g group, larger volume of seven structures in the 70 pg/g group and smaller volume of one structure in the 700 pg/g group. No cerebral or retinal vascular differences were detected. Overall, neonatal PGF replacement altered behavior and neuroanatomy of adult Pgf mice.
子痫前期妊娠的后代存在认知改变。胎盘生长因子（PGF）在子痫前期水平降低；水平降低可能会影响大脑发育。PGF 基因敲除小鼠在脑血管、神经解剖和行为方面与正常同基因对照存在差异。我们使用脑成像和行为测试，询问在发育上不同步（即新生儿期）时补充 PGF 是否会改变成年 Pgf 小鼠的血管、神经解剖和/或行为状态。在出生后第 1-10 天，通过腹膜内注射将 C57BL/6-Pgf 幼仔用载体或 10pg/g、70pg/g 或 700pg/g 的 PGF 处理。这些小鼠接受行为测试和 MRI 灌注以及视网膜血管分析。第二组用载体或 PGF 处理的小鼠进行微 CT 成像灌注。与载体处理的小鼠相比，10pg/g PGF 处理的小鼠表现出更少的运动活动和更大的焦虑样行为。抑郁样行为呈性别特异性、剂量依赖性降低，700pg/g PGF 处理的雌性小鼠相对于载体处理的雌性小鼠降低最明显。空间学习没有差异。MRI 显示，10pg/g 组的三个结构体积较小，70pg/g 组的七个结构体积较大，700pg/g 组的一个结构体积较小。未检测到脑或视网膜血管差异。总体而言，新生期 PGF 替代改变了成年 Pgf 小鼠的行为和神经解剖。
