Aberrant Resting-state In An Overexpressing MicroRNA-30e Rat Model Of Cognitive Impairment

Objective:Cognitive impairments is one of the clinical features widely exist in many neuropsychiated disorder.Despite numbers studies, Cognitive impairments complex etiology and pathogenesis remains unknown. More and more studies suggest that cognitive impairment may be related to function alternation of some brain regions activation or some distance region function disconnectivity. In this study we use Re Ho approach and Granger causality model analysis Function Magnetic resonance imaging datas, try to find some abnormal function region or abnormal function connectivity between region.Methods:Twenty-four 4 weeks SD rats were random divided into four groups: control group,sham group,cognitive impairment model group and fluoxetine group. The normal group rats do not any treatments. The 1ul lentivirus particle carrying the mi RNA-30 e was injected into the bilaterally hippocampal DG of rats to construct the overexpressing micro RNA-30 e model. In sham- operated group rats, bilateral hippocampal DG injected with Lenti-GFP was used to rule out abnormal behavior cause by surgery hippocampal damage. Two weeks after surgery, 8 of the 16 mi RNA-30 e transfected rats were randomly assigned to the fluoxetine group and administered by gastric intubation of fluoxetine for 14 consecutive days(10mg/kg per day).The other three groups rats received equivalent amounts of sterile saline at same time.Two weeks later after administration, we use Morris water maze test and open field test to evaluate whether mi RNA-30 e gene transfected rat have Cognitive impairments-like behaviors. MRI scan employe one week later, We used a regional homogeneity(Re Ho) approach to analyze resting-state f MRI data to explore the changes of regional synchronization. We then used Granger causality analysis to explore function connectivity between the hippocampus, striatum and thalamus.Results:1) The escape latency and total travel distance and time was significantly increase in rats transfected with mi RNA-30 e compared with control and sham-surgery groups,meanwhile, fluoxetine treatment can reversed the above changes.2) Re Ho in the right hippocampus and striatum cortex were higher in overexpressing model groups,no Re Ho significant decrease was found.3) One-way Granger causality connections was observed between thalamus and hippocampus in model group rather than the One-way Granger causality connections from thalamus to striatum in normal rats. After fluoxetine treatment, we found thalamushippocampus-striatum One-way Granger causality connections.Conclusion:Results from this study support the hypothesis that Cognitive impairments is a disorder of disrupted local functionality. Characteristics of local spontaneou actixity in mi RNA-30 e transfected rats can provide further evidence for image-based diagnosis and for investigating the pathogenesis of Cognitive impairments.