Inhibition of FLT1 Attenuates Neurodevelopmental Abnormalities and Cognitive Impairment in Offspring Caused by...

Fms-like tyrosine kinase 1 (FLT1) has been shown to regulate processes such as angiogenesis, neurogenesis, and cognitive impairment. However, the role of FLT1 in prenatal stress (PS) is unclear. The purpose of this study was to investigate the role of FLT1 in PS mothers and their offspring. Wire mesh restrainers were used to construct PS rat model. The levels of FLT1, IL-1β, IL-6, and ROS in clinical samples and rat samples were detected by qRT-PCR, ELisa kit, and DCFH-DA fluorescence kit. Morris water maze assay and forced swimming assay were used to test the cognitive function of offspring young rats. The apoptosis level of hippocampal neurons and the expression of NMDARs were detected by MTT assay, TUNEL assay, and Western blot. The results showed that FLT1 was upregulated in PS mothers and positively correlated with PS degree. The level of FLT1 was elevated in PS model rats. Knockdown of FLT1 reduced maternal ROS and MDA levels and increased SOD levels in PS rats. Knockdown of FLT1 also reduced the secretion of IL-1β, IL-6, and cortisol in PS rats. Inhibition of FTL1 alleviated cognitive impairment in PS offspring pups. Inhibition of FTL1 reduced hippocampal neuronal apoptosis and increased the expression of NMDARs in PS progeny. In conclusions, we demonstrated that knockdown of FLT1 inhibits maternal oxidative stress, inflammation, and cortisol secretion in PS rats. In addition, knockdown of FLT1 also alleviated cognitive dysfunction and neurodevelopmental abnormalities in PS offspring pups.