Early Changes Of Hippocampal Metabolite In Animal Model Of Alzheimer's Disease Measured By 9.4T MRS

AIM: To study the metabolite alteration in hippocampi of Alzheimer's mice by using in vitro 9.4T high resolution magnetic resonance spectroscopy, and explore the possibility of biomarkers at early stage of AD.METHODS: Thirty-six KunMing mice were randomly divided into five experimental groups and one control group. The experimental groups were subcutaneously injected with D-galactose(120mg/d·kg)and sodium nitrite (NaNO2) (90mg/d·kg) daily.The injections were started at the same day for all of mice. Mice of the five experimental groups were injected respectively for 30 days, 40 days, 50 days, 60 days and 70 days, while the control group was injected with saline for 70 days. Each group was subjected to the Morris water maze test (MWM) after finishing the injection. 24 hours later after Morris water maze test,mice were sacrificed and the hippocampi were removed. The right hippocampus was grinded into powder for 1H-MRS examination and the left hippocampus was sliced and stained for histopathological examination. The concentrations of metabolites including NAA (N-acetylaspartate), Glu (glutamate), mI (myo-inositol) and Cho (choine) were analyzed.RESULTS: MWM test showed a decrease in the spatial learning and memory on 70 day campared to control (P<0.05). Histopathology confirmed the neuronal loss, amyloid plaques and neurofibrillary tangles in the hippocampi at the last two time points. The mean concentration of NAA was 3.04±0.28μmol/g, and Glu was 4.00±0.47μmol/g in the control mice. NAA and Glu concentrations were decreased on days 30 and 40. The concentrations of NAA and Glu decreased by 60.2% and 67% respectively on day 40 compared to control (p<0.01). Following day 40, NAA and Glu concentrations both increased, but still remained lower than the control group on day 50. On days 60 and 70, the concentrations of NAA and Glu decreased again. The decrease of both NAA (1.82±0.48μmol/g) and Glu (1.81±0.57μmol/g) became statistically significant on day 70 (P<0.05). In contrast, no differences at any time were found for the concentrations of mI and Cho compared to the control group.CONCLUSION: Alzheimer's mice can be induced by injecting with D-galactose and sodium nitrite. 1H-MRS is a useful tool for observing the changing trend of metabolites. NAA and Glu decreasing may be the biomarkers for the early stage of AD.