模拟极端高原环境对大鼠海马转录组的影响

doi:10.16098/j.issn.0529-1356.2024.04.010

解剖学报 ›› 2024, Vol. 55 ›› Issue (4): 445-451.doi: 10.16098/j.issn.0529-1356.2024.04.010

模拟极端高原环境对大鼠海马转录组的影响

方璇¹汪涛²程全成¹刘怀存¹张艳¹南燕¹陈春花¹张卫光^1*

1.北京大学基础医学院人体解剖学与组织学胚胎学系，北京 100083; 2.北京大学国际医院2020级临床医学，北京 102206

收稿日期:2024-03-29 修回日期:2024-04-10 出版日期:2024-08-06 发布日期:2024-08-06
通讯作者: 张卫光 E-mail:zhangwg@bjmu.edu.cn
基金资助:
科技创新2030-重大项目

Effects of simulated extreme plateau environment on hippocampal transcriptome in rats

FANG Xuan¹ WAGN Tao² CHENG Quan-cheng¹ LIU Huai-cun¹ ZHANG Yan¹ NAN Yan¹ CHEN Chun-hua¹ ZHANG Wei-guang^1*

1. Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University, Beijing 100083, China; 2.Class 2020 of Clinical Medicine, Peking Univeristy International Hospital, Beijing 102206, China

Received:2024-03-29 Revised:2024-04-10 Online:2024-08-06 Published:2024-08-06
Contact: ZHANG Wei-guang E-mail:zhangwg@bjmu.edu.cn
Supported by:
Science and Technology Innovation 2030 Major Projects

摘要/Abstract

摘要：

目的建立极端高原低压低氧环境急性暴露模型，探讨与大鼠学习记忆损伤相关的转录组学的变化。方法选取6周龄、200~250 g健康雄性SD大鼠，分为对照组和高原组。对照组经常压常氧处理（19只），高原组置于低压低氧舱内（19只），模拟8000米海拔高度，处理72 h。每组取16只，利用场景恐惧和Morris水迷宫实验（各8只）检测行为学变化。每组取3只，全部海马组织提取RNA行转录组学测序，通过基因本体论（GO）、京都基因与基因组百科全书（KEGG）和基因集富集分析（GSEA）分析极端高原环境诱导学习记忆损伤的分子机制。结果行为学结果显示，与对照组相比，高原组大鼠恐惧记忆和空间学习记忆能力下降。GO和KEGG分析显示，极端高原环境重塑海马组织微环境，影响细胞间信号传递，GSEA显示，极端高原环境上调与质膜和细胞外基质相关的基因集。结论 8000米海拔的极端高原环境通过影响大鼠海马组织微环境，破坏细胞间连接，损害细胞间通讯，进而诱导学习记忆功能损伤。

关键词: 高原, 低压低氧, 学习, 记忆, 微环境, 细胞通讯, Morris水迷宫实验, 大鼠

Abstract:

Objective To establish an acute exposure model of extreme plateau hypobaric hypoxia environment and explore transcriptomic changes related to learning and memory impairment in rats. Methods Healthy male SD rats aged 6-weeks, 200-250 g, were selected and divided into control group and plateau group. The control group was treated with normal pressure and oxygen (19 rats), and the plateau group was placed in a hypobaric hypoxia chamber (19 rats) at a simulated altitude of 8000 meters and treated for 72 hours. Behavioral changes were detected with 16 animals from each group using contextual fear conditioning and Morris water maze (8 rats each). Three hippocampal tissues were extracted from each group for transcriptomic sequencing, and the molecular mechanism of learning and memory impairment induced by extreme plateau environment was analyzed by Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes(KEGG) and gene set enrichment analysis(GSEA) enrichment. Results The behavioral result showed that compared with the control group, the fear memory and spatial learning memory abilities of rats in plateau group were decreased. GO and KEGG analyses showed that the extreme altitude environment reshaped the hippocampal microenvironment and affected the intercellular signal transmission, while GSEA analysis showed that the extreme altitude environment up-regulated the gene set related to the plasma membrane and extracellular matrix. Conclusion The extreme plateau environment at an altitude of 8000 meters could affect the microenvironment of rat hippocampus, destroy intercellular connections and impair intercellular communication and then induce learning and memory impairment.

Key words: Plateau, Hypobaric hypoxia, Learn, Memorize, Microenvironment, Cell communication, Morris water maze, Rat

中图分类号:

方璇汪涛程全成刘怀存张艳南燕陈春花张卫光. 模拟极端高原环境对大鼠海马转录组的影响[J]. 解剖学报, 2024, 55(4): 445-451.

FANG Xuan WAGN Tao CHENG Quan-cheng LIU Huai-cun ZHANG Yan NAN Yan CHEN Chun-hua ZHANG Wei-guang. Effects of simulated extreme plateau environment on hippocampal transcriptome in rats[J]. Acta Anatomica Sinica, 2024, 55(4): 445-451.

参考文献

［1］Sharma P, Mohanty S, Ahmad Y. A study of survival strategies for improving acclimatization of lowlanders at high-altitude［J］. Heliyon, 2023, 9(4): e14929.

［2］Ni XY. Railway passenger transport in and out of Tibet reached a record high in 2023［N］. Qinghai Daily, 2024, 004. (in Chinese)

倪晓颖. 2023年铁路进出藏旅客运送量创历史新高［N］. 青海日报, 2024, 004.

［3］Pun M, Guadagni V, Bettauer KM, et al. Effects on cognitive functioning of acute, subacute and repeated exposures to high altitude［J］. Front Physiol, 2018, 9: 1131.

［4］Churilova A, Zachepilo T, Baranova K, et al. Differences in the autophagy response to hypoxia in the hippocampus and neocortex of rats［J］. Int J Mol Sci, 2022, 23(14): 8002.

［5］Yang XY, Geng LA, Li RH, et al. Huperzine A-Liposomes efficiently improve neural injury in the hippocampus of mice with chronic intermittent hypoxia［J］. Int J Nanomed, 2023, 18: 843-859.

［6］Spahic H, Parmar P, Miller S, et al. Dysregulation of ErbB4 signaling pathway in the dorsal hippocampus after neonatal hypoxia-ischemia and late deficits in PV+ interneurons, synaptic plasticity and working memory［J］. Int J Mol Sci, 2023, 24(1): 508.

［7］Christiansen L, Urbin MA, Mitchell GS, et al. Acute intermittent hypoxia enhances corticospinal synaptic plasticity in humans［J］. Elife, 2018, 7: e34304.

［8］Goussakov I, Synowiec S, Aksenov DP, et al. Occlusion of activity dependent synaptic plasticity by late hypoxic long term potentiation after neonatal intermittent hypoxia［J］. Exp Neurol, 2021, 337: 113575.

［9］Matott MP, Hasser EM, Kline DD. Sustained hypoxia alters nts glutamatergic signaling and expression and function of excitatory amino acid transporters［J］. Neuroscience, 2020, 430: 131-140.

［10］Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2［J］. Genome Biol, 2014, 15(12): 550.

［11］Song JQ, Ma Zh, Zeng Z, et al. Characteristics analysis of blood routine and blood biochemical examination of officers and soldiers in a unit stationed at 4500 m plateau for a long time［J］. People’s Military Surgeon, 2021, 64(9): 801-804. (in Chinese)

宋佳琪, 马振, 曾泽, 等. 某部长期驻4500 m高原官兵血常规及血生化检查特点分析［J］. 人民军医, 2021, 64(9): 801-804.

［12］Xu HF, Lei Q, Wang HM, et al. Analysis of blood biochemical index detection results of the medical personnel of the training troops at an altitude of 5000 meters［J］. Chinese Journal of Modern Medicine, 2023, 25(7): 40-44. (in Chinese)

徐海峰, 雷权, 王辉明, 等. 海拔5000米驻训部队就诊人员血液生化指标检测结果分析［J］. 中国现代医药杂志, 2023, 25(7): 40-44.

［13］Aboouf MA, Thiersch M, Soliz J, et al. The brain at high altitude: from molecular signaling to cognitive performance［J］. Int J Mol Sci, 2023, 24(12): 10179.

［14］Zola-Morgan S, Squire LR, Rempel NL, et al. Enduring memory impairment in monkeys after ischemic damage to the hippocampus［J］. J Neurosci, 1992, 12(7): 2582-2596.

［15］Tang W, Meng Z, Li N, et al. Roles of gut microbiota in the regulation of hippocampal plasticity, inflammation, and hippocampus-dependent behaviors［J］. Front Cell Infect Microbiol, 2021, 10: 611014.

［16］Scoville WB, Milner B. Loss of recent memory after bilateral hippocampal lesions［J］. J Neurol Neurosurg Psychiatry, 1957, 20(1): 11-21.

［17］Peng YY, Yin HC, Li S, et al. Transcriptome of pituitary function changes in rat model of high altitude cerebral edema［J］. Genomics, 2022, 114(6): 110519.

［18］Koester-Hegmann C, Bengoetxea H, Kosenkov D, et al. High-altitude cognitive impairment is prevented by enriched environment including exercise via VEGF signaling［J］. Front Cell Neurosci, 2019, 12: 532.

［19］Buss EW, Corbett NJ, Roberts JG, et al. Cognitive aging is associated with redistribution of synaptic weights in the hippocampus［J］. Proc Natl Acad Sci USA, 2021, 118(8): e1921481118.

［20］Kanehisa M, Araki M, Goto S, et al. KEGG for linking genomes to life and the environment［J］. Nucleic Acids Res, 2008, 36 (Database issue): D480-D484.

［21］Khan A, Fornes O, Stigliani A,et al. JASPAR 2018: update of the open-access database of transcription factor binding profiles and its web framework［J］. Nucleic Acids Res, 2018, 46(D1): D260-D266.

［22］Thornton C, Leaw B, Mallard C, et al. Cell death in the developing brain after hypoxia-ischemia［J］. Front Cell Neurosci, 2017, 11: 248.

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模拟极端高原环境对大鼠海马转录组的影响

Effects of simulated extreme plateau environment on hippocampal transcriptome in rats

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