快速老化模型小鼠海马组织间液中单胺类神经递质水平的昼夜节律变化和增龄变化  

Circadian rhythm and aging changes in monoamine neurotransmitters in hippocampal interstitial fluid of senescence-accelerated mice

作　　者：王静 程肖蕊 周文霞 张永祥 王淑美 WANG Jing;CHENG Xiao-rui;ZHOU Wen-xia;ZHANG Yong-xiang;WANG Shu-mei(College of Traditional Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou 510006,China;State Key Laboratory of Toxicology and Medical Countermeasures,Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China)

机构地区：[1]广东药科大学中药学院,广东 广州 510006 [2]军事科学院军事医学研究院毒物药物研究所,抗毒药物与毒理学国家重点实验室,北京 100850

出　　处：《中国药理学与毒理学杂志》2019年第11期933-940,共8页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金(81473191);国家自然科学基金(30973541)。

摘　　要：目的检测快速老化模型小鼠(SAM)海马组织间液中单胺类神经递质及其代谢产物水平的昼夜节律变化和增龄变化。方法采用微透析技术,分别在12∶00,16∶00,20∶00,24∶00及次日4∶00和8∶00采集3,6,9,12,15和18月龄快速老化亚系小鼠(SAMP8)和抗快速老化亚系小鼠(SAMR1)海马组织间液,用高效液相色谱(HPLC)-电化学方法测定组织间液中单胺类神经递质去甲肾上腺素(NE)、多巴胺(DA)及其代谢产物3,4-二羟基苯乙酸(DOPAC)和高香草酸(HVA)、5-羟色胺(5-HT)及其代谢产物5-羟吲哚乙酸(5-HIAA)的水平。结果①昼夜节律:与同月龄SAMR1相比,SAMP8海马组织间液中NE、DA及其代谢产物HVA和DOPAC、5-HT及其代谢产物5-HIAA浓度的昼夜节律发生紊乱。②增龄性变化:3~18月龄SAMP8海马组织间液中NE总含量增龄性变化与SAMR1相似。3~12月龄SAMP8 DA及其代谢产物DOPAC总含量增龄性变化与SAMR1相似;DA代谢产物HVA总含量除3月龄外,6~18月龄与SAMR1相似。3~18月龄SAMP85-HT总含量增龄性变化,除18月龄外,与SAMR1相似;5-HT代谢产物5-HIAA总含量除6月龄外,与SAMR1相似。结论与同月龄SAMR1相比,SAMP8海马组织间液中NE、DA及其代谢产物DOPAC和HVA、5-HT及其代谢产物5-HIAA水平的昼夜节律发生紊乱,增龄性变化与SAMR1基本相似,提示单胺类神经递质昼夜节律紊乱可能是导致SAMP8中枢学习记忆功能进行性快速衰退的机制之一。OBJECTIVE To investigate the circadian rhythm and age-related changes of mono?amine neurotransmitters and their metabolites in hippocampal tissue fluid in senescence-accelerated mice(SAM).METHODS Microdialysis technology was used to collect hippocampal tissue fluid in SAM prone 8(SAMP8)and its control of age-matched SAM resistance 1(SAMR1)at 12∶00,16∶00,20∶00,24∶00 and 4∶00 and 8∶00 on the next day.The HPLC-ECD technique was used to determine the monoamine levels including norepinephrine(NE),dopamine(DA)and its metabolic product 3,4-dihy?droxy phenylacetic acid(DOPAC)and homovanillic acid(HVA),serotonin(5-HT)and its metabolite product 5-hydroxy indole acetic acid(5-HIAA).RESULTS①Circadian rhythm:compared with SAMR1 of the same age,the circadian rhythms of NE,DA and their metabolites HVA,DOPAC,5-HT and their metabolites 5-HIAA were disordered in the hippocampal interstitial fluid of SAMP8.②Age-related changes:the age-related changes in NE content in the hippocampal interstitial fluid of SAMP8 aged 3 to 18 months were similar to those of SAMR1.The age-related changes in DA and DOPAC in SAMP8 were similor to those of SAMR1 at 3 to 12 month.The total content of HVA was similar to that of SAMR1 at 6-18 months except at 3 months.The total content of 5-HT was similar between SAMP8 and SAMR1 aged 3 to 18 months except for 18 months,and the total content of 5-HIAA was similar to that of SAMR1 except for 6 months.CONCLUSION Compared with SAMR1,the circadian rhythms of NE,DA,DOPAC,HVA,5-HT and 5-HIAA in the hippocampal interstitial fluid of SAMP8 are disordered.The aging changes in SAMP8 are similar to those of SAMR1,suggesting that the circadian rhythms of monoamine neurotransmitters are one of the mechanisms leading to the progressive decline of cogni?tion in SAMP8.

关 键 词：快速老化模型小鼠 海马 微透析 去甲肾上腺素 多巴胺 5-羟色胺 

分 类 号：R964[医药卫生—药理学]