摘要
睡眠障碍是临床中的常见多发病,睡眠障碍易诱发和加重认知障碍疾病,损害海马依赖的学习记忆功能。光疗是一种改善睡眠的有效方法,鉴于此,本课题组研究了光疗对睡眠剥夺小鼠炎症反应、氧化应激反应及BDNF-TrkB信号通路的影响,探索光疗对睡眠剥夺小鼠学习记忆的影响。通过旋转圆筒法建立睡眠剥夺模型,小鼠随机被分为对照组、睡眠剥夺组、光疗组(468nm,光照强度分别为100,300,900lx)。光疗组边剥夺边治疗,每天早晚进行光照30 min,于剥夺3d后对各组小鼠进行水迷宫实验和旷场实验,采用ELISA法检测小鼠血浆和海马组织中TNF-α、SOD、5-HT因子的表达量,采用RT-PCR法检测小鼠BDNF、TrkB和Akt中的mRNA表达量。结果显示:与对照组相比,睡眠剥夺导致小鼠体重下降,游泳潜伏期增长,促进了炎性因子TNF-α的表达,降低了SOD活性和5-HT的表达,并降低了BDNF、TrkB和Akt中的mRNA表达;与睡眠剥夺组相比,光疗组小鼠的游泳潜伏期缩短,平台交叉次数增多,TNF-α表达下降,SOD和5-HT表达呈上升趋势,焦虑样行为减轻,BDNF、TrkB与Akt中的mRNA表达升高;300lx光照剂量的效果较为显著。光疗可以修复睡眠剥夺引起的氧化应激损伤,调节炎症反应,促进BDNF表达,代偿相对较短时间的睡眠剥夺,保护自身的认知能力,缓解睡眠剥夺引起的学习记忆缺陷。
Objective With the accelerating pace of life,the pressure is getting bigger and bigger,and people are threatened by sleep deprivation because of lack of sleep.Hippocampus is closely related to memory function.Prolonged sleep deprivation tends to damage the hippocampus,leading to reduced learning and memory capacity,depressed mood,reduced immune function,and a range of mental illnesses.Presently,the main treatments for sleep deprivation are sedative drugs and acupuncture in Chinese medicine.Recently,phototherapy has been widely studied for its advantages of non-invasive,safe,and fewer side effects,and it can regulate the biological rhythm.Therefore,this study investigated the effects of light therapy on the inflammatory response,oxidative stress,and BDNF-TrkB signaling pathway in sleep-deprived mice and discussed the effects of phototherapy on learning and memory of sleep-deprived mice,providing a clinical basis for the regulation of sleep disorders using light therapy.Methods In this study,mice were trained in a water maze for six days for learning and memory skills,which was mainly divided into navigation experiment and space search experiment.Finally,the swimming latency and the times of crossing the original platform were recorded.Then the sleep deprivation model was established by rotating the cylinder,and the mice were randomly divided into the control group,sleep deprivation group,and phototherapy group(468 nm,100 lx,300 lx,and 900 lx).The phototherapy group was treated during deprivation.Every morning and evening,the mice in each group were illuminated for 30 min.After deprivation for three days,the mice in each group were weighed and recorded.Then,behavioral experiments were conducted:water maze experiment and open field experiment.The learning and memory degree of mice was tested using water maze test,and the anxiety and depression degree of mice was tested using the open field test.After that,the brain tissue of mice was sampled,and the expression levels of TNF-α,SOD,and 5-HT factors in plasma and hippocampus of mice were detected using ELISA.RT-PCR was used to detect the gene expression of BDNF,TrkB,and Akt in mice.Results and Discussions The results showed that compared with the control group,sleep deprivation resulted in the weight loss of mice(Fig.2).The water maze test showed that the swimming latency of sleep-deprived mice increased,the number of platform crossings decreased(Table 2),and the activity of the mice in the target quadrant reduced(Fig.3),suggesting that memory was impaired in mice.Open field experiments showed that the percentage of time in the central area of sleep-deprived mice in the total area decreased(Fig.4),the spontaneous activity of mice decreased,and anxiety was obvious.At the same time,sleep deprivation resulted in reduced 5-HT expression in plasma and hippocampus(Fig.5),increased TNF-α expression,and reduced SOD expression(Fig.6),also,it reduced the gene expressions of BDNF,TrkB,and Akt(Fig.7).After the phototherapy intervention,the phototherapy group mice had a slight increase in body weight,and the swimming latency of the phototherapy group was shorter,the number of platform crossings was higher(Table 2),and the percentage of time spent active in the target quadrant increased(Fig.3).The time percentage of the central area in the total area of mice was increased(Fig.4),and the anxiety-like behavior of mice was alleviated.The expression of 5-HT showed an upward trend(Fig.5),which played an antidepressant role and relieved the anxiety state of mice.The expression of the inflammatory factor TNF-α decreased,which reduced the occurrence of inflammatory reaction,and the expression of antioxidant enzyme activity in mice increased(Fig.6),which might mitigate the oxidative stress damage caused by sleep deprivation.The mRNA expression of BDNF,TrkB,and Akt increased(Fig.7).BDNF enhanced synaptic plasticity,possibly by activating the Akt pathway after binding to TrkB receptors,enhancing learning,and memory functions.Overall,the effect of the 300 lx light dose was significant.Conclusions In this study,we investigated the effects of phototherapy on the learning and memory abilities of sleep-deprived mice by establishing a sleep deprivation model.We discovered that sleep deprivation significantly decreased the learning and memory abilities of mice and produced anxiety-like behaviors,while the combination of 468 nm blue light treatment prevented the increase of inflammatory response,improved the antioxidant capacity of hippocampal tissue,regulated the expression of BDNF-TrkB signaling pathway genes,enhanced inter-synaptic transmission,and effectively improved the learning and memory abilities of mice.
作者
陈洪丽
高静静
姜忠迪
王仲朋
陈龙
明东
Chen Hongli;Gao Jingjing;Jiang Zhongdi;Wang Zhongpeng;Chen Long;Ming Dong(Academy of Medical Engineering and Translational Medicine,Tianjin University,Tianjin 300072,China;School of Life Sciences,Tiangong University,Tianjin 300387,China)
出处
《中国激光》
EI
CAS
CSCD
北大核心
2022年第5期224-234,共11页
Chinese Journal of Lasers
基金
国家自然科学基金(61705164,81630051)
天津市“项目+团队”重点培养专项(XB202007)
天津市自然科学基金(19JCQNJC01600)。
关键词
医用光学
光疗
睡眠剥夺
氧化应激
学习记忆
突触可塑性
medical optics
phototherapy
sleep deprivation
oxidative stress
learning and memory
synaptic plasticity
