Effects of Long-term Intervention of Adenosine A1 Receptor Antagonist on Cognitive Function in Alzheimer's Disease Model Mice
Objective To investigate the effects of long-term intervention of adenosine A1 receptor antagonist DPCPX on cognitive function related electrophysiological indexes,behavioral performance and pathological examination in Alzheimer's dis-ease(AD)model mice.Methods Seven-month-old C57BL/6J and APP/PS1 mice were randomly divided into C57-control group,C57-DPCPX group,APP/PS1-control group and APP/PS1-DPCPX group.DPCPX(1 mg/kg·d)or control vehicle was injected intraperitoneally for 21 consecutive days.The Plexon system was used to record local field potential in the hippocampus CA1 re-gion of mice.MATLAB software was used to evaluate the characteristics of sharp wave ripples(SWRs),which were a type of electrophysiological index related to hippocampal cognitive function.Morris water maze was used to evaluate the spatial memory ability of mice.Immunofluorescence staining was used to detect Aβ plaque deposition in the hippocampus.Results The cogni-tive function related electrophysiological indexes(SWRs),behavioral performance(Morris water maze)and Aβ pathological ex-amination of the four groups of mice were analyzed.The results were as follows:(1)As for the average number and average du-ration of SWRs,there was no significant differences between the C57-control group and the C57-DPCPX group,and between the APP/PS1-control group and the APP/PS1-DPCPX group(both P＞0.05),only the results in C57-control group were signifi-cantly higher than those in APP/PS1-control group(P=0.0019,P=0.0202).(2)In Morris water maze experiment,there was no significant difference in escape latency during learning phase between the C57-control group and the C57-DPCPX group mice,and between the APP/PS1-control group and the APP/PS1-DPCPX group(both P＞0.05),only the results in C57-control group were significantly shorter than those in APP/PS1-control group(P＜0.05).In the exploration stage,no statistical differ-ence was found in the platform crossing times and the target quadrant residence time ratio between the C57-control group and the C57-DPCPX group,and between the APP/PS1-control group and the APP/PS1-DPCPX group(both P＞0.05),only the re-sults of C57-control group were significantly higher than those in APP/PS1-control group(P=0.0024,P=0.0415).(3)On the number and area of Aβ plaques,there were no significant differences between APP/PS1-control group and APP/PS1-DPCPX group mice(both P＞0.05).Conclusion Long-term intervention of adenosine A1 receptor antagonist DPCPX can not signifi-cantly improve the cognitive function of AD model mice.It is suggested that it may be difficult to achieve significant improve-ment in cognitive function with a single target intervention.
Alzheimer's diseaseadenosine A1 receptorsharp wave ripplescognitive functionlocal field poten-tial
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