丰富环境促进缺氧缺血性脑损伤幼鼠髓鞘发育并改善神经功能

易烜宇, 贺雨, 艾青, 余卫红, 王计, 史源

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重庆医科大学学报 ›› 2024, Vol. 49 ›› Issue (03) : 246-253. DOI: 10.13406/j.cnki.cyxb.003459
基础研究

丰富环境促进缺氧缺血性脑损伤幼鼠髓鞘发育并改善神经功能

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The role of environmental enrichment in promoting myelin formation and neural function in hypoxic-ischemic brain injury

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摘要

目的 探索丰富环境(environmental enrichment,EE)干预对缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)幼鼠神经功能、脑室旁白质及海马髓鞘相关蛋白表达的影响。 方法 取7 d SD大鼠随机分为假手术组(Sham组)、模型组+标准环境组(HIBD+SE组)及模型组+丰富环境组(HIBD+EE组),采用Rice-Vannucci法制备HIBD模型。Sham组及HIBD+SE组不予任何干预饲养于标准环境中,HIBD+EE组于术后8 d至术后18 d予以丰富环境干预处理。术后18 d采用Morris水迷宫定位航行实验测定平台区穿梭次数,采用Western blot检测脑室旁白质及海马区髓鞘生成相关蛋白尿苷二磷酸糖基转移酶8(recombinant UDP glycosyltransferase 8,UGT8)、少突胶质细胞转录因子2(oligodendrocyte transcription factor 2,OLIG2)的表达,采用RT-qPCR检测脑室旁白质及海马区UGT8、OLIG2、糖脂转运蛋白(glycolipid transfer protein,GLTP)、髓鞘转录因子(myelin regulatory factor Gene,MYRF)的表达水平,采用免疫组化法检测神经元核(neuronal nuclei antigen,NeuN)表达水平,采用免疫荧光检测胼胝体髓鞘标志(myelin basic protein,MBP)表达水平。 结果 术后18 d,与HIBD+SE组比较,HIBD+EE组穿越平台次数增多(P<0.01),HIBD+EE组较HIBD+SE组脑室旁白质及海马区UGT8 mRNA及蛋白表达升高(P<0.05),脑室周围白质及海马区OLIG2、GLTP、MYRF mRNA表达升高(P<0.05),海马CA1区NeuN表达水平高于HIBD+SE组(P<0.05),胼胝体MBP平均荧光强度高于HIBD+SE组(P<0.05)。 结论 丰富环境能促进缺氧缺血性脑损伤新生大鼠少突胶质细胞谱系分化、髓鞘发育,改善学习记忆能力,可能与上调脑室周围白质及海马区UGT8蛋白表达,增加神经元分化成熟细胞数量有关。

Abstract

Objective To explore the effects of environmental enrichment(EE) on neural function,myelin-related protein expression of periventricular white matter and hippocampus in rats with hypoxic-ischemic brain injury(HIBD). Method Seven-day-old SD rats were randomly divided into sham surgery group,model+standard environment group(HIBD+SE group) and model + environmental enrichment group(HIBD+EE group),and the HIBD model was established with the Rice-Vannucci method. The sham surgery group and the standard environment group were raised in the standard environment without any intervention,and the environmental enrichment group was treated with enriched environment from 8 to 18 days after surgery. At day18 after the surgery,Morris water maze was used to determine the escape latency of finding the hidden platform. Western blot was used to detect the expression of UGT8,a myelination-related protein,in periventricular white matter and hippocampus,and expression of oligodendrocyte differentiation gene OLIG2. RT-qPCR was used to detect the mRNA expression levels of OLIG2、GLTP、MYRF、UGT8 in periventricular white matter and hippocampus. Immunohistochemistry was used to detect the expression levels of NeuN,and immunofluorescence was used to detect the expression of myelin basic protein(MBP) in the corpus callosum. Result At 18 days after surgery,compared with HIBD+SE group,platform crossing times of the HIBD+EE group increased(P<0.01). The HIBD+EE group showed higher expression of UGT8 mRNA and protein in the periventricular white matter and hippocampus compared to HIBD+SE group(P<0.05). The expression of OLIG2,GLTP,MYRF mRNA in the periventricular white matter and hippocampus increased(P<0.05),and the expression of NeuN in CA1 region was higher than that of HIBD+SE group(P<0.01),the fluorescent intensity of MBP in corpus callosum region was higher than that in standard environment group(P<0.05). Conclusion Environmental enrichment promotes the differentiation of oligodendrocyte lineages and myelin development in neonatal rats with HIBD,and improves learning and memory ability,which may be related to up-regulating UGT8 protein expression in periventricular white matter and hippocampus and increasing the number of neuronal mature cells.

关键词

丰富环境 / 脑白质损伤 / 空间记忆能力

Key words

environmental enrichment / white matter injury / spatial memory capabilities

中图分类号

R72

引用本文

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易烜宇 , 贺雨 , 艾青 , . 丰富环境促进缺氧缺血性脑损伤幼鼠髓鞘发育并改善神经功能. 重庆医科大学学报. 2024, 49(03): 246-253 https://doi.org/10.13406/j.cnki.cyxb.003459
Yi Xuanyu, He Yu, Ai Qing, et al. The role of environmental enrichment in promoting myelin formation and neural function in hypoxic-ischemic brain injury[J]. Journal of Chongqing Medical University. 2024, 49(03): 246-253 https://doi.org/10.13406/j.cnki.cyxb.003459

参考文献

1
Min YJ Ling EG Li F. Immunomodulatory mechanism and potential therapies for perinatal hypoxic-ischemic brain damage[J]. Front Pharmacol202011:580428.
2
Zhao J He L Yin LL. lncRNA NEAT1 binds to miR-339-5p to increase HOXA1 and alleviate ischemic brain damage in neonatal mice[J]. Mol Ther Nucleic Acids202020:117-127.
3
Liu ZX Yan MB Liang YJ,et al. Nucleoporin Seh1 interacts with Olig2/Brd7 to promote oligodendrocyte differentiation and myelination[J]. Neuron2019102(3):587-601.
4
Ismail TR Yap CG Naidu R,et al. Enrichment protocol for rat models[J]. Curr Protoc20211(6):e152.
5
Kempermann G. Environmental enrichment,new neurons and the neurobiology of individuality[J]. Nat Rev Neurosci201920(4):235-245.
6
Thamizhoviya G Vanisree AJ. Enriched environment enhances the myelin regulatory factor by mTOR signaling and protects the myelin membrane against oxidative damage in rats exposed to chronic immobilization stress[J]. Neurochem Res202146(12):3314-3324.
7
Rice JE 3rd Vannucci RC Brierley JB. The influence of immaturity on hypoxic-ischemic brain damage in the rat[J]. Ann Neurol19819(2):131-141.
8
Bieber M Gronewold J Scharf AC,et al. Validity and reliability of neurological scores in mice exposed to middle cerebral artery occlusion[J]. Stroke201950(10):2875-2882.
9
Xie Y Zhang XH Xu PF,et al. Aberrant oligodendroglial LDL receptor orchestrates demyelination in chronic cerebral ischemia[J]. J Clin Invest2021131(1):e128114.
10
Schneider J Miller SP. Preterm brain Injury:white matter injury[J]. Handb Clin Neurol2019162:155-172.
11
Harlow HF Suomi SJ. Nature of love:simplified[J]. Am Psychol197025(2):161-168.
12
Ohline SM Abraham WC. Environmental enrichment effects on synaptic and cellular physiology of hippocampal neurons[J]. Neuropharmacology2019145:3-12.
13
Jin XH Li T Zhang LN,et al. Environmental enrichment improves spatial learning and memory in vascular dementia rats with activation of Wnt/β-catenin signal pathway[J]. Med Sci Monit201723:207-215.
14
Gusel’nikova VV Korzhevskiy DE. NeuN As a neuronal nuclear antigen and neuron differentiation marker[J]. Acta Naturae20157(2):42-47.
15
Wang HY Hsieh PF Huang DF,et al. RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function[J]. Sci Rep20155:17383.
16
Poulos AM Thompson RF. Localization and characterization of an essential associative memory trace in the mammalian brain[J]. Brain Res20151621:252-259.
17
Cahoy JD Emery B Kaushal A,et al. A transcriptome database for astrocytes,neurons,and oligodendrocytes:a new resource for understanding brain development and function[J]. J Neurosci200828(1):264-278.
18
Duncan GJ Plemel JR Assinck P,et al. Myelin regulatory factor drives remyelination in multiple sclerosis[J]. Acta Neuropathol2017134(3):403-422.
19
Emery B Agalliu D Cahoy JD,et al. Myelin gene regulatory factor is a critical transcriptional regulator required for CNS myelination[J]. Cell2009138(1):172-185.
20
Davis DL Mahawar U Pope VS,et al. Dynamics of sphingolipids and the serine palmitoyltransferase complex in rat oligodendrocytes during myelination[J]. J Lipid Res202061(4):505-522.
21
Yang F Guan YD Feng X,et al. Proteomics of the corpus callosum to identify novel factors involved in hypomyelinated Niemann-Pick Type C disease mice[J]. Mol Brain201912(1):17.
22
Dupree JL Suzuki K Popko B. Galactolipids in the formation and function of the myelin sheath[J]. Microsc Res Tech199841(5):431-440.
23
Forbes TA Goldstein EZ Dupree JL,et al. Environmental enrichment ameliorates perinatal brain injury and promotes functional white matter recovery[J]. Nat Commun202011(1):964.
24
苑爱云,孙向峰,侯 梅,等. 丰富环境对缺氧缺血脑损伤幼鼠空间记忆能力及海马区BDNF、自噬相关蛋白LC3表达的影响[J]. 中国康复医学杂志202035(11):1296-1301.
Yuan AY Sun XF Hou M,et al. Effects of environmental enrichment on the expressions of brain-derived neurotrophic factor and microtubule-associated protein 1 light chain 3 type in the hippocampus of immature rats with hypoxic-ischemic brain damage[J]. Chin J Rehabil Med202035(11):1296-1301.
25
宋名杨,朱路文,叶 涛,等. 丰富环境对缺血缺氧脑损伤新生大鼠海马脑源性神经营养因子表达及细胞凋亡的影响[J]. 中国康复医学杂志201732(7):750-755.
Song MY Zhu LW Ye T,et al. Effects of enriched environment intervention on brain-derived neurotrophic factor expression and apoptosis in hippocampus of hypoxic ischemic brain damaged neonatal rats[J]. Chin J Rehabil Med201732(7):750-755.

基金

国家重点研发计划资助项目(2022YFC2704802)
科技人才与平台计划(院士专家工作站)资助项目(202305AF150098)

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