Relationship between CSF inflow into the cerebral glymphatic system of AD mice and age:A visualization study based on 9.4 T DCE-MRI
Objective:To explore the changes of cerebrospinal fluid(CSF)inflow into the cerebral glymphatic system(GS)in Alzheimer's disease(AD)model mice at different ages via 9.4 T dynamic contrast-enhanced(DCE)-MRI,in order to elucidate the alterations through the cerebral GS clearance with age,and the role of aquaporin 4(AQP4)in the cerebral GS clearance.Materials and Methods:APP/PS1 AD mice and wild-type(WT)mice aged 2,4,6,and 8 months were included in a total of 8 groups,with 1 mouse in each group.After injection of gadolinium contrast agent Gadopentate dimeglumine(Gd-DTPA)into the cerebellomedullary cistern,the first DCE-MRI scan was completed at 30 minutes,followed by collection every 15 minutes until a total of 8 imaging scans were completed.Subsequently,AQP4 inhibitor N-(1,3,4-thiadiazole)nicotinamide(TGN-020)was used to treat WT mice aged 2 months before DCE scanning.Immunofluorescence assay was used to detect the expression changes of AQP4 and β-amyloid protein with increasing age.Results:In the early stage of AD of the APP/PS1 mouse model,it was observed that with increasing age,amyloid protein gradually accumulated,and mean signal intensity of CSF inflow showed an initial increase followed by a decrease.At 4 to 6 months of age,the deposition rate of β-amyloid protein was slow,corresponding to the highest mean signal intensity of CSF inflow at corresponding age(CSF inflow at 4 months old,2 711.67±1 270.25;CSF inflow at 6 months old,2 632.25±729.65).Meanwhile,AQP4 exhibited a decreasing polarization degree with increasing age.Subsequently,after treatment with AQP4 inhibitor TGN-020,a decrease in mean signal intensity of CSF inflow was observed in the GS(from 3 578.08±1 199.95 to 1 655.42±377.96;P=0.06).Conclusions:In the early stage of AD disease(before 8 months of age),the utilization of the cerebral GS is more pronounced in 6-month-old mice,which may serve as a window period for AD treatment.AQP4 plays an important role in the cerebral GS and may be a breakthrough point for studying and treating AD.
cerebral glymphatic systemAlzheimer's disease9.4 T magnetic resonance imagingdynamic contrast-enhanced magnetic resonance imagingaquaporin 4(AQP4)APP/PS1 mouse model
国家科技期刊平台
NSTL
万方数据
维普
