Intervention effects of miR-125b-5p on cognitive dysfunction induced by traumatic brain injury in rats and its mechanisms

Abstract

To investigate the effects and molecular mechanisms of miR-125b-5p on cognitive dysfunction caused by traumatic brain injury (TBI). The rats were randomly divided into control group, TBI group (model group), NC Agomir group (false negative group) and miR-125b-5p agomir group (high expression group), with 5 rats in each group. The false negative group and the high expression group were injected with NC agomir and miR-125b-5p agomir, respectively. The brain injury model was established by modified Feeney method except control group. Animal behavioral experiments were utilized for evaluation of the motor coordination, learning and memory and the degree of nerve damage in rats; and enzyme-linked immunosorbent assays (ELISA) and Western blot (WB) were used for determination of the expression levels of inflammatory factors and nerve-related factors in the hippocampus of rats in each group respectively. Finally, combined with bioinformatics, downstream target genes of miR-125b-5p were predicted and verified by reverse transcription polymerase chain reaction (RT-PCR) and WB. Compared with control group, mir-125b-5p expression level, motor coordination ability, learning and memory ability, brain-derived neurotrophic factor(BDNF) and nerve growth factor(NGF) expression levels of rats in model group and false negative group were decreased significantly, the MNSS score, the expressions of interleukins (IL-1β, IL 6), tumor necrosis factor-α(TNF-α) and glial fibrillary acid protein(GFAF) were increased significantly (P＜0.01);However, compared with model group and false negative group, the above situation of rats in high expression group was opposite (P＜0.01). Bioassay showed that MMP-15 was the downstream target gene of miR-125b-5p. Compared with the control group, the expression of MMP-15 in model group and false negative group was increased significantly (P＜0.01);Compared with model group and false negative group, the expression of MMP-15 in high expression group was decreased significantly (P＜0.01) . miR-125b-5p can improve cognitive dysfunction induced by TBI in rats, which may be related to regulating the expression level of MMP-15, thereby inhibiting the neuroinflammatory response after TBI and promoting neuronal regeneration.