Song Shuang, Guo Ruoyi, Guo Jiangyuan, Li Bin, Han Yusen, Zhang Huining, Guo Li
Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Key Neurological Laboratory of Hebei Province, Shijiazhuang, Hebei, China.
Brain Behav. 2025 May;15(5):e70525. doi: 10.1002/brb3.70525.
To investigate whether nicotinamide adenine dinucleotide (NAD+) supplementation can improve behavioral changes in a cuprizone-intoxicated mouse model.
Six-week-old C57BL/6J mice were divided into three groups: two were fed 0.2% cuprizone chow (cuprizone and cuprizone + NAD+ groups), and the other group was fed normal rodent chow (control group) for 4 weeks. The mice in the cuprizone + NAD+ group received 250 mg/kg/day NAD+ intraperitoneally once a day, while the other mice were administered saline simultaneously. Behavioral tests for spatial memory (Morris water maze and Y maze), locomotor ability (grip test and rotarod test), depression-like behavior (open field test and tail suspension test), and exploratory behavior (open field test) were conducted.
In the probe test of the Morris water maze, the cuprizone group spent a significantly smaller proportion of time in the target quadrant than the control group did (16.32% vs. 31.66%, p = 0.006). However, supplementation with NAD+ increased the value (28.78% vs. 16.32%, p = 0.023). Similarly, in the Y maze test, the cuprizone group demonstrated a notably lower ratio of effective alterations compared to the control group (0.543 vs. 0.648, p < 0.001), and the cuprizone + NAD+ group presented an improved ratio compared with the cuprizone group (0.613 vs. 0.543, p = 0.021). Compared with the control group, cuprizone toxicity resulted in a decreased time to fall (169.10 vs. 247.60 s, p = 0.015) in the grip test, but NAD+ supplementation mitigated this effect (261.60 vs. 169.10 s, p = 0.003). There were no significant differences in the immobile time among groups in both the tail suspension test and the open field test, and there were also no significant differences in center distance in the open field test.
Direct NAD+ supplementation improves the locomotor ability and spatial memory of cuprizone-intoxicated C57BL/6J mice. However, NAD+ supplementation does not show significant effects on depressive and exploratory behavior of experimental mice.
研究补充烟酰胺腺嘌呤二核苷酸（NAD+）是否能改善用双环己酮草酰二腙诱导中毒的小鼠模型的行为变化。
将6周龄的C57BL/6J小鼠分为三组：两组喂食含0.2%双环己酮草酰二腙的饲料（双环己酮草酰二腙组和双环己酮草酰二腙+NAD+组），另一组喂食正常啮齿动物饲料（对照组），持续4周。双环己酮草酰二腙+NAD+组的小鼠每天腹腔注射一次250mg/kg/天的NAD+，而其他小鼠同时注射生理盐水。进行了空间记忆（莫里斯水迷宫和Y迷宫）、运动能力（握力测试和转棒试验）、抑郁样行为（旷场试验和悬尾试验）以及探索行为（旷场试验）的行为测试。
在莫里斯水迷宫的探针试验中，双环己酮草酰二腙组在目标象限花费的时间比例显著低于对照组（16.32%对31.66%，p = 0.006）。然而，补充NAD+提高了该值（28.78%对16.32%，p = 0.023）。同样，在Y迷宫试验中，双环己酮草酰二腙组的有效交替率明显低于对照组（0.543对0.648，p < 0.001），且双环己酮草酰二腙+NAD+组与双环己酮草酰二腙组相比交替率有所提高（0.613对0.543，p = 0.021）。与对照组相比，双环己酮草酰二腙毒性导致握力测试中的跌落时间减少（169.10对247.60秒，p = 0.015），但补充NAD+减轻了这种影响（261.60对169.10秒，p = 0.003）。在悬尾试验和旷场试验中，各组之间的不动时间没有显著差异，在旷场试验中的中心距离也没有显著差异。
直接补充NAD+可改善双环己酮草酰二腙诱导中毒的C57BL/6J小鼠的运动能力和空间记忆。然而，补充NAD+对实验小鼠的抑郁和探索行为没有显著影响。
