Study on inhibitory effect of GC-miR-143 inhibitor nanoparticles on D2 receptor-mediated neurological behavioral damage in lacunar infarction

Abstract

Blocking the dopamine D2 receptor is a key link in anti-psychiatric disease. Knockdown of miR-143 improved neurological behavioral damage by regulating the D2 receptor signaling pathway. The risk of neurological behavior damage can be increased 20 times by 1–2 lacunar infarction lesions. Based on the fact that miR-143 can target and regulate the D2 receptor signaling pathway, this study focused on analyzing the inhibitory effect of GC-miR-143 inhibitor nanoparticles on neurological behavior damage in lacunar infarction. 60 SD rats were separated into sham operation, model, vehicle, vehicle+inhibitor, inhibitor, or D2 agonist group (n = 10). The vascular dementia (VD) model was made by ligating bilateral common carotid arteries. Morris water maze assessed rats behavioral changes. Quantitative Real-Time Reverse Transcription PCR (QRT-PCR) was applied to detect levels of miRNA-143. Proteins were extracted from the prefrontal cortex, and immunoblotting was performed to measure the downstream of signal proteins of Neuregulin 1 (NRG1) and D2 receptor signaling pathways, p-protein kinase B (AKT) and p-Glycogen Synthase Kinase 3β (GSK3β). On days 1 to 5 of the water maze experiment, the escape latency for the five groups of rats were longer than in sham group; while escape latency for vehicle+inhibitor group and inhibitor group was shorter. Compared to VD model rats, vehicle+inhibitor group and inhibitor group had significantly reduced escape latency. Cross-platform time number for five groups was decreased and it was increased in vehicle+inhibitor group and inhibitor group with decreased number for D2 agonist group w. Compared with D2 agonist group, the vehicle+inhibitor group and inhibitor group showed more cross-platform times. Compared to sham operation group, levels of NRG1, p-AKT/GSK3β in remaining five groups were significantly decreased. Their levels in vector+inhibition group and inhibitor group were dramatically up-regulated, and levels of the above-mentioned proteins in D2 agonist group were significantly decreased. Their levels in vector+inhibitor group and inhibitor group were up-regulated relative to D2 agonist group. The GC-miR-143 inhibitor nanoparticles can up-regulate the expression of NRG1 and antagonize the D2 receptor to weaken the inhibitory effect of D2 receptor-mediated signaling pathways and inhibit neurological behavioral damage in lacunar cerebral infarction.