Regulatory role of microRNA-30b and plasminogen activator inhibitor-1 in the pathogenesis of cognitive impairment

Abstract

The present study aimed to investigate the role of plasminogen activator inhibitor-1 (PAI-1) in drug-induced early cognitive impairment and the underlying mechanism concerning microRNA (miR)-30b. A mouse model of cognitive impairment was established by intraperitoneal injection of scopolamine (2 mg/kg body weight) for 13 days. Behavioral performance was assessed using the Morris water maze (MWM) test. The mRNA expression levels of PAI-1 and miR-30b were detected using quantitative polymerase chain reaction (qPCR). The protein expression levels of PAI-1 in the hippocampus and blood were determined using western blot analysis and enzyme-linked immunosorbent assays. The MWM test demonstrated that, on days 3 and 4, the escape latency was significantly elevated in the model mice in comparison with control group (P<0.05). In addition, the length of swimming path was significantly increased (P<0.05), while the number of times of crossing the platform location was significantly reduced in the model mouse group (P<0.05) in comparison with the control group. qPCR demonstrated that the mRNA expression levels of PAI-1 in the model mice was significantly elevated in the hippocampus and blood in comparison with the control group (P<0.01). Furthermore, western blot analysis and enzyme-linked immunosorbent assay demonstrated that the protein expression levels of PAI-1 were significantly elevated in the hippocampus and blood in the model group, in comparison with the control group (P<0.05). Notably, the levels of miR-30b in the hippocampus and blood were significantly decreased in the model mice in comparison with the control group (P<0.01). To conclude, the expression levels of PAI-1 were significantly elevated in mice with scopolamine-induced cognitive impairment, which may be associated with the downregulation of miR-30b. The findings from the present study suggest that miR-30b may be involved in the regulation of PAI-1, which would contribute to the pathogenesis of cognitive impairment.

Keywords: cognitive impairment; microRNA-30b; plasminogen activator inhibitor-1.

Figure 1.

Declined learning and memory function of scopolamine-treated mice. The behavioral performance was assessed using the Morris water maze test. (A) The escape latency and the probe test evaluating (B) the length of swimming path and (C) the times of crossing the platform location. *P<0.05, **P<0.01 vs. the control group.

Figure 2.

Increased PAI-1 expression levels in the hippocampal and blood tissues in model mice. The mRNA expression levels of PAI-1 in the (A) hippocampus and (B) blood were determined by quantitative polymerase chain reaction. The protein expression levels of PAI-1 in the (C) hippocampus and (D) blood were detected using western blot analysis and enzyme-linked immunosorbent assay. *P<0.05, **P<0.01 vs. the control group. PAI-1, plasminogen activator inhibitor-1.

Figure 3.

Bioinformatic analysis of the upstream regulators of plasminogen activator inhibitor-1. miR, microRNA.

Figure 4.

Decreased miR-30b levels in the hippocampus and blood of model mice. The levels of miR-30b in the (A) hippocampal and (B) blood tissues were determined by the reverse transcription-quantitative polymerase chain reaction. **P<0.01 vs. the control group. miR, microRNA.