摘要
目的抑郁的发生机制不清及药物的临床疗效不佳,导致其成为世界难题。已有研究发现甲醛的气态暴露或液态腹腔注射都可直接诱发小鼠抑郁样行为,而内源甲醛是否参与抑郁的发生尚不清楚。本研究探索脂多糖(lipopolysaccharide,LPS)是否通过刺激内源甲醛产生而诱发小鼠抑郁的分子机制;并观察非侵入物理疗法——630 nm红光照射是否能激活甲醛脱氢酶而降解甲醛,从而改善小鼠抑郁样行为。方法雄性成年C57BL/6J小鼠随机分组:a.对照组,腹腔注射磷酸缓冲液(phosphate buffer solution,PBS);b.抑郁模型组,按浓度梯度腹腔注射LPS;c.红光干预组,按浓度梯度腹腔注射LPS后并定时进行630 nm全身红光照射。采用旷场实验(open field test,OFT)、糖水偏爱(suorose preference test,SPT)、悬尾实验(tail suspension test,TST)、强迫游泳(forced swimming test,FST)等方法,评估小鼠的抑郁样行为;用甲醛荧光(Na-FA,特异甲醛荧光探针)定量法及整脑甲醛荧光成像法,检测小鼠脑组织甲醛浓度及分布;用酶联免疫吸附测定(ELISA)试剂盒检测IL-1β、TNF-α、IL-6、氨基脲敏感胺氧化酶(SSAO)浓度。结果LPS急性注射1 h后小鼠全脑,特别是中脑中,甲醛急剧蓄积;并伴随IL-1β、TNF-α、IL-6含量上升;24 h即出现抑郁样行为,包括:旷场总运动距离、中心区运动时间(距离)显著减少;悬尾实验、强迫游泳实验总不动时间显著增加。而630 nm红光治疗显著改善LPS诱发的小鼠抑郁样行为,并伴随中脑炎症因子IL-1β、TNF-α、IL-6水平下降。结论中脑甲醛蓄积是抑郁发生的触发因素,诱发了炎症因子大量释放,而非侵入物理疗法——红光照射消除蓄积的甲醛,是一种有前景的无创治疗抑郁新策略。
Objective The unclear mechanism of depression occurrence and the undesired clinical efficacy of drugs are the difficult problems all over the world.Previous studies have found that gaseous formaldehyde(FA)exposure or intraperitoneal injection of FA can directly induce depression-like behaviors in mice.Whether endogenous FA leads to depression is unclear.This study was to explore whether lipopolysaccharide(LPS)induces depression-like behaviors in mice by stimulating endogenous FA generation,and to observe whether noninvasive physical therapy——630 nm red light irradiation can activate FA dehydrogenase and degrade FA,thereby attenuate depression-like behaviors in mice.Methods Male adult C57BL/6J mice were randomly divided into:(1)control group,intraperitoneal injection of phosphate buffered saline(PBS);(2)depression model group,intraperitoneal injection of LPS at a concentration gradient;(3)red light intervention group,these mice were intraperitoneally injected with LPS and treated with 630 nm red light irradiation.The depression-like behaviors of mice were evaluated by open field test,sucrose preference test,tail suspension test and forced swimming test.The concentration and distribution of FA in brain tissue of mice were detected by FA fluorescence(Na-FA,specific FA fluorescent probe)quantitative method and whole brain FA fluorescence imaging.The concentrations of IL-1β,TNF-α,IL-6 and semicarbazide-sensitive amine oxidase(SSAO)were detected by ELISA.Results One hour after acute injection of LPS,FA accumulated rapidly in the whole brain,especially in the midbrain.With the increase of IL-1βand TNF-αcontent;24-hour depression-like behaviors,for example,open field total movement distance,central area movement time(distance)decreased significantly;the total immobility time of tail suspension test and forced swimming test were increased.However,630 nm red light treatment significantly attenuated LPS-induced depression-like behavior in mice accompanied by a decrease in midbrain inflammatory factors IL-1βand TNF-
作者
赵丹睿
张凤吉
刘懿莹
吴一箐
赵夯
廖海康
潘文浩
程建华
童志前
ZHAO Dan-Rui;ZHANG Feng-Ji;LIU Yi-Ying;WU Yi-Qing;ZHAO Hang;LIAO Hai-Kang;PAN Wen-Hao;CHENG Jian-Hua;TONG Zhi-Qian(School of Mental Health,Institute of Aging,The First Affiliated Hospital,Wenzhou Medical University,Key Laboratory of Alzheimer’s Disease of Zhejiang Province,Oujiang Laboratory,Wenzhou 325035,China)
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2023年第7期1664-1676,共13页
Progress In Biochemistry and Biophysics
基金
国家自然科学基金(82071214)
北京自然科学基金(M21004)
国家级大学生创新创业训练计划项目(202210343033)资助。
