早年应激致雌性大鼠认知功能障碍中脑脊液氨基酸变化及意义  

CHANGES OF AMINO ACID PROFILES IN CEREBRO-SPINAL FLUID IN FEMALE RATS WITH COGNITIVE DYSFUNCTION CAUSED BY EARLY LIFE STRESS

作　　者：王笑天 谢方 王雪[1] 王世达 赵云[1] 钱令嘉 WANG Xiao-tian;XIE Fang;WANG Xue;WANG Shi-da;ZHAO Yun;QIAN Ling-jia(Institute of Military Cognition and Brain Sciences,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China)

机构地区：[1]军事科学院军事医学研究院军事认知与脑科学研究所,北京100850

出　　处：《营养学报》2022年第2期164-172,共9页Acta Nutrimenta Sinica

基　　金：国防基础科研计划重点项目(No.JCKY2019548B001)。

摘　　要：目的 研究母婴分离应激雌性大鼠成年后脑脊液(cerebro-spinal fluid,CSF)氨基酸的变化,为探索早年应激致认知障碍的发生机制提供新的科学依据。方法 采用母婴分离(maternal separation,MS)应激的方法建立早年应激大鼠模型,随机分对照组(CON)和应激组(MS)。在实验大鼠成年后采用旷场、物体识别及水迷宫实验评价认知功能,尼氏染色观察脑海马和前额叶皮质区神经细胞数量及排列,全自动蛋白表达分析系统(WESTM)检测突触后致密物95(PSD-95)蛋白表达水平,超高效液相色谱-串联质谱(UPLC-MS/MS)靶向定量分析大鼠脑脊液氨基酸含量。结果 与CON组大鼠相比,MS组大鼠旷场评分、物体识别认知指数、水迷宫穿台次数显著降低(P<0.01),水迷宫寻台时间显著延长(P<0.001),海马CA3区、前额叶皮质区神经细胞排列疏松,数量明显减少(P<0.05),海马、前额叶皮质突触可塑性蛋白标记物PDS-95表达水平明显降低(P<0.05、P<0.01)。MS组大鼠脑脊液中筛选具有潜在生物学效应的氨基酸为苏氨酸(P<0.05,|log2FC|>0)。结论 母婴分离应激致大鼠成年后认知功能障碍,脑相关区域损伤和脑脊液氨基酸代谢异常,以及苏氨酸水平降低影响神经细胞突触可塑性可能是应激性认知功能障碍的病理基础。[营养学报,2022,44(2):164-172]Objective The changes of amino acid profiles in cerebro-spinal fluid(CFS) of female rats after maternal separation(MS) stress were studied, so as to provide a new scientific basis for exploring the mechanism of cognitive impairment induced by early life stress. Methods Rats were randomly divided into control group(CON) and stress group(MS). The model of early life stress was established by maternal separation. After adulthood, the cognitive function was evaluated by open-field test, object recognition test and Morris water maze. The number and arrangement of nerve cells in hippocampus and prefrontal cortex were observed after Nissl staining. The protein expression of postsynaptic density 95(PSD-95) was detected by automatic protein expression analysis system(WESTM). The amino acid profiles in cerebrospinal fluid were determined by ultra high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS). Results Compared with the CON group, the open-field score, the object recognition cognitive index and the times of crossing the platform in the Morris water maze in the MS group were significantly lower(P<0.001). The distribution of nerve cells in the CA3 and prefrontal cortex of the hippocampus was loosely arranged and the number of neurons was significantly diminished(P<0.05). The expression of PDS-95, a protein marker of synaptic plasticity in hippocampus and prefrontal cortex, was decreased significantly(P<0.05, 0.01). Threonine was found to be the amino acid with potential biological effect in cerebro-spinal fluid of rats in the MS group.(P<0.05 and |log2FC|> 0). Conclusion The cognitive impairment in adult rats caused by maternal separation stress, the damage of brain cognitive related areas and the abnormal profiles of amino acids in cerebrospinal fluid, and the influenced the decreased threonine level on synaptic plasticity of nerve cells may be the pathological basis of stress cognitive impairment. [ACTA NUTRIMENTA SINICA, 2022, 44(2):164-172]

关 键 词：早年应激 雌性大鼠 脑脊液 氨基酸代谢 突触可塑性 认知障碍 

分 类 号：R151.1[医药卫生—营养与食品卫生学]