摘要
Abstract
OBJECTIVE To investigate the protective effects of hydroxytyrosol hydroxybutyrate(HTHB)against cognitive impairment induced by acute sleep deprivation in mice and to explore the underlying mechanisms.METHODS Male C57BL/6J mice were assigned to the following groups:normal control,normal groups administered with HTHB 30,60 and 120 mg·kg-1 or hydroxytyrosol(HT 19.25,38.5 and 77 mg·kg-1),a sleep deprivation(SD)model group,and SD groups co-administered with the same doses of HTHB or HT.Acute sleep deprivation was induced for 72-96 h using a rotarod apparatus in all groups except the normal control and normal drug-treated groups.Based on dose-response assess-ments in the Y-maze and novel object recognition tests,the effective doses(HTHB 60 mg·kg-1 and HT 38.5 mg·kg-1)were selected for subsequent evaluation in the two-choice visual discrimination task that was performed in a subset of groups:normal control,normal+HTHB 60 mg·kg-1,normal+HT 38.5 mg·kg1,SD model,SD+HTHB 60 mg·kg-1,and SD+HT 38.5 mg·kg-1.Cognitive functions that were assessed included spatial working memory(Y-maze spontaneous alternation),object recognition memory(novel object recognition)and visual discrimination ability(two-choice visual discrimination task).Biochemically,levels of hippocampal reactive oxygen species(ROS)were quantified by ELISA while the ATP content was determined using a firefly luciferase-based assay.RESULTS In non-sleep-deprived mice,neither HTHB nor HT administration significantly altered locomotor activity,spatial working memory,object recognition memory,or visual discrimination performance.Following sleep deprivation,the model group displayed significant cognitive deficits,including reduced spontaneous alternation rate,lower novel object recognition indexes,and decreased accuracy in the visual discrimination task at 48 and 96 h.These impairments were accompanied by elevated hippocampal ROS levels and reduced ATP contents com-pared to the control group.Treatment with HT 38.5 and 77 mg·kg-1 significantly attenuated the deficit in spontaneous alternation,but did not affect other parameters.In contrast,HTHB at 60 and 120 mg·kg-1 produced broader restorative effects and significantly reversed impairment in both spontaneous alterna-tion and novel object recognition.Furthermore,HTHB at 60 mg·kg-1 significantly improved visual discrimination accuracy at 48 and 96 h,while lowering hippocampal ROS levels and increasing ATP contents.CONCLUSION HTHB effectively mitigates acute sleep deprivation-induced impairment in spatial working memory,object recognition memory,and visual discrimination in mice.This protection is likely mediated by the enhancement of mitochondrial antioxidant capacity and the restoration of energy metabolism.关键词
羟基酪醇羟丁酸酯/羟基酪醇/急性睡眠剥夺/认知功能/线粒体功能/氧化应激Key words
hydroxytyrosol hydroxybutyrate/hydroxytyrosol/acute sleep deprivation/cognitive function/mitochondrial function/oxidative stress分类
药学
