| Background and objective:Alzheimer’s disease(AD)is a neurological disease that is the most common cause of dementia in the elderly.Dexmedetomidine(Dex)is an α2-adrenergic receptor agonist with potential neuroprotective,hemodynamic stabilizing,and anesthetic protective effects.MicroRNAs(miRNAs)are involved in the pathophysiology of AD and have important biomarker potential.Therefore,in this study,we focused on the specific molecular regulatory mechanism of miR-214-5p during Dex treatment of AD mice in order to explore the molecular mechanism by which Dex exerts neuroprotection during AD progression.Methods:1.The differences of miRNA expression between AD patients and normal controls were analyzed by miRNA microarray,and the miR-214-5p expression levels in plasma and cerebrospinal fluid were further collected,and the correlation between miR-214-5p expression levels in cerebrospinal fluid and Aβ42 was investigated.2.AD model mice were constructed,and Morris water maze test was used to evaluate AD mice.The learning and memory,spatial orientation and cognitive levels of AD mice were evaluated after transfection with overexpressed miR-214-5p and silencing SUZ12;HE staining,Nissl staining and TUNEL staining were used to stain the neuropathological damage of hippocampal tissue;ELISA was used to evaluate the inflammatory level in the CA1 region of the hippocampus;finally,qPCR was used to analyze the miR-214-5p expression level.3 used biological databases to predict the targets of miR-214-5p,qPCR was used to analyze SUZ12 expression levels in plasma and cerebrospinal fluid of AD patients,and Pearson correlation coefficient was used to analyze the correlation between SUZ12 and miR-214-5p and Aβ42.Dual-luciferase reporter assay and RNA pull down were used to analyze the targeting binding relationship between miR-214-5p and SUZ12,and the hypothesis was validated in vivo assays.Results:1 qPCR results indicated that miR-214-5p expression was significantly decreased in plasma and cerebrospinal fluid of AD patients(P<0.01).The results of Pearson correlation analysis revealed a positive correlation between miR-214-5p expression levels and Aβ42 content in the cerebrospinal fluid of AD patients(r-0.4637,P0.039).2 Compared with the control group,the mean escape latency of mice in the AD group trained for 5 days was significantly longer than that of the control group(P<0.05),the percentage of time spent in the target quadrant was significantly shorter(P<0.05),and the time to pass the platform within 60 seconds was significantly shorter(P<0.05).The results of pathological staining showed that neuronal loss and apoptosis were severe in the CA1 region of the hippocampus in AD mice compared with the normal control group;ELISA results indicated that IL-6,TNF-α,and MDA levels were significantly increased and SOD levels were significantly decreased in AD mice.MiR-214-5p was significantly decreased in AD mice,and treatment of AD mice with Dex improved nerve injury and reduced hippocampal CA1 inflammation levels,and transfection with MiR-214-5p mimic enhanced the therapeutic effect of Dex.3 The potential target of miR-214-5p may be SUZ12,and SUZ12 expression was significantly elevated in AD patients compared with controls(P<0.01).Pearson analysis indicated that SUZ12 was negatively correlated with miR-214-5p expression levels(r=-0.7927,P<0.001)and negatively correlated with Aβ42 content(r=0.8026,P<0.001)in the cerebrospinal fluid of AD patients.Dual-luciferase reporter assay and RNA pull down results confirmed that there was an interaction between SUZ12 and miR-214-5p.Transfection of AD mice with shSUZ12 and Dex treatment enhanced the therapeutic effect,and overexpression of SUZ12 reversed the effect of miR-214-5p mimic Dex treatment effect.Conclusion:1 The expression of miR-214-5p is significantly decreased and SUZ12 is significantly increased in the cerebrospinal fluid of AD patients;2 Dex treatment can significantly improve the cognitive ability of AD mice,alleviate neuronal injury and apoptosis in the CA1 region of the hippocampus,and reduce inflammatory parameters in the brain tissue;3 Dex may have a potential neuroprotective effect on AD through the miR-214-5p/SUZ12 axis.This study provides a new therapeutic target for AD treatment. |
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