[Effect of inhibiting miR-204 expression on the learning and memory abilities of neonatal rats with intrauterine growth restriction and related mechanism].

Objectives: To investigate the effect of inhibiting miR-204 expression on the learning and memory abilities of neonatal rats with intrauterine growth restriction (IUGR) and related mechanism.

Methods: A rat model of IUGR was prepared by low-protein diet. The 3-day-old IUGR rats were divided into three groups: model, miRNA antagonist control and miR-204 antagonist, with 10 rats in each group. Ten normal neonatal rats served as the control group. Morris water maze test was used to measure the learning and memory abilities of the rats. Quantitative real-time PCR was used to measure the mRNA expression levels of miR-204 and brain-derived neurotrophic factor (BDNF) in the hippocampus. Nissl staining and TUNEL staining were used to observe the number of Nissl bodies and the apoptosis of cells in the hippocampus. Western blot was used to measure the expression levels of BDNF/TrkB signaling pathway-related proteins in the hippocampus.

Results: Compared with the control group, the model group had a significant increase in the escape latency and a significant reduction in the number of platform crossings (<0.001). The model group also had significant increases in the apoptosis rate of cells and the expression level of miR-204 in hippocampal tissue (<0.001), while the number of Nissl bodies, the mRNA expression level of BDNF, and the protein expression levels of BDNF, p-TrkB, and p-CREB in the model group were significantly reduced compared with the control group (<0.001). After inhibition of the expression of miR-204, the number of Nissl bodies, the mRNA expression level of BDNF, and the protein expression levels of BDNF, p-TrkB, and p-CREB significantly increased, while the cell apoptosis rate and the expression level of miR-204 in the hippocampus significantly decreased. The escape latency was also reduced, while the number of platform crossings increased after inhibition of the expression of miR-204 (<0.001).

Conclusions: Inhibiting miR-204 can improve the learning and memory functions of neonatal rats with IUGR, possibly by targeted activation of the BDNF/TrkB signaling pathway.