Simulated high altitude hypoxia induces anxiety- and depression-like behaviors in mice

Jinghui ZHAO; Lian WANG; Rui XIAO; Ruotong RUAN; Tianyao LIU; Xin LI; Yun CAI; Xiaotang FAN

doi:10.16016/j.1000-5404.202103142

您当前的位置：

首页 >

文章列表页 >

Simulated high altitude hypoxia induces anxiety- and depression-like behaviors in mice

Basic Medicine | 更新时间：2026-01-09

- Simulated high altitude hypoxia induces anxiety- and depression-like behaviors in mice
- Journal of Third Military Medical University Vol. 43, Issue 18, Pages: 1806-1812(2021)
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)医学心理系军事认知心理学教研室
- 作者简介：
- 基金信息：
  
  the Open Topics in Key Laboratories of MOE for Extreme Environmental Medicine(KL2019GY003);the Military Medical Pre-Research Project Fund of Army Medical University(2018XYY08)
- DOI：10.16016/j.1000-5404.202103142
  CLC： R339.54;R363.274;R749.4
- Received：18 March 2021，
  
  Revised：2021-06-11，
  
  Published：30 September 2021
- 稿件说明：
移动端阅览
Jinghui ZHAO, Lian WANG, Rui XIAO, et al. Simulated high altitude hypoxia induces anxiety- and depression-like behaviors in mice[J]. Journal of Third Military Medical University, 2021, 43(18): 1806-1812.
DOI：

Jinghui ZHAO, Lian WANG, Rui XIAO, et al. Simulated high altitude hypoxia induces anxiety- and depression-like behaviors in mice[J]. Journal of Third Military Medical University, 2021, 43(18): 1806-1812. DOI： 10.16016/j.1000-5404.202103142.

摘要

目的

探讨模拟高原缺氧条件对小鼠焦虑样行为以及抑郁样行为的影响。

方法

选用C57成年雄性小鼠，分为3组(

=10)：平原对照组，24 h高原缺氧组，7 d高原缺氧组。行为学方法检测小鼠焦虑样行为、小鼠短期记忆以及小鼠抑郁样行为；免疫组化检测小鼠下丘脑室旁核C-Fos、AVP和GR免疫反应阳性细胞数量；酶联免疫吸附测定(enzyme linked immunosorbent assay，ELISA)法检测血液中促肾上腺皮质激素(adrenocorticotropic hormone

ACTH)、皮质酮浓度。

结果

高架十字迷宫实验结果表明7 d高原缺氧组小鼠与对照组相比，开臂时间百分比下降，焦虑样行为增加。悬尾实验表明，7 d高原缺氧组小鼠与对照组相比不动时间增多，抑郁样行为增加(

0.01)。强迫游泳实验结果显示，24 h高原缺氧处理组小鼠不动时间较对照组显著增加，抑郁样行为增加(

0.05)。免疫组化结果表明：7 d高原缺氧组小鼠下丘脑室旁核C-Fos蛋白被明显激活。7 d高原缺氧处理小鼠下丘脑室旁核AVP神经元数量、GR阳性数量增加(

0.01)；7 d高原缺氧组小鼠与对照组小鼠相比血液ACTH浓度升高(

0.05)、24 h高原缺氧处理组小鼠皮质酮浓度上升(

0.05)。

结论

急进高原会引起小鼠焦虑和抑郁样行为，且下丘脑-垂体-肾上腺轴对该应激反应进行调节。

Abstract

Objective

To determine the effects of simulated altitude hypoxia conditions on anxiety- and depression-like behaviors in mice.

Methods

C57 adult male mice were divided into 3 groups (

=10): plain control group

24 h plateau hypoxia group

and 7 d plateau hypoxia group. Behavioral observations were used to detect anxiety-like behaviors

short-term memory

and depression-like behaviors in the mice. Immunohistochemical assay was applied to measure the number of C-Fos

AVP and GR immunoreactive cells in the paraventricular nucleus of the hypothalamus. Enzyme linked immunosorbent assay (ELISA) was adopted to detect the concentrations of adrenocorticotropic hormone (ACTH) and corticosterone in the blood.

Results

The Results of the elevated plus maze test showed that the mice in the 7 d plateau hypoxia group had a lower percentage of open arm time and increased anxiety-like behavior than those of the cont

rol group. Tail suspension test indicated that the mice of the 7 d plateau hypoxia group had more immobile time and increased depression-like behavior than those of the control group (

0.01). In the forced swimming test

the 24 h hypoxia group had significantly longer immobility time and increased depression-like behavior than the control group (

0.05). Immunohistochemical assay showed that the C-Fos protein in the paraventricular nucleus of the hypothalamus was significantly activated in the 7-d plateau hypoxia group. The numbers of AVP and GR positive neurons were increased in the paraventricular nucleus of the hypothalamus in the 7 d plateau hypoxia group (

0.01). Compared with the control group

the ACTH concentration of mice was elevated in the 7 d plateau hypoxia group (

0.05)

so was the corticosterone concentration in the mice in the 24 h plateau hypoxia group (

0.05).

Conclusion

Rapidly entering the high altitude can cause anxiety- and depression-like behaviors in mice

and the stress responses are regulated by the hypothalamic-pituitary-adrenal axis.

关键词

Keywords

references

黄琴, 关巍, 冯喜英. 高原环境对肺组织的影响[J]. 临床肺科杂志, 2014, 19(9): 1696-1698, 1699. DOI: 10.3969/j.issn.1009-6663.2014.09.050.

HUANGQ, GUAN W, FENG X Y. The influence of high altitude environment on lung tissue[J]. J Clin Pulm Med, 2014, 19(9): 1696-1698, 1699. DOI: 10.3969/j.issn.1009-6663.2014.09.050.

胡光涛, 陈许波, 杨柳, 等. 高原驻训军人抑郁情绪与心理应激、心理弹性的相关性[J]. 西南国防医药, 2019, 29 (4): 485-487. DOI: 10.3969/j.issn.10040188.2019.04.030.

HU G T,CHEN X B, YANG L, et al . Correlation of depression with psychological stress and resilience of soldiers stationed at high altitude[J ] . Med J Natl Defending Forces Southwest China, 2019, 29(4): 485-487. DOI: 10.3969/j.issn.1004-0188.2019.04.030.

廉国锋, 李锏, 罗勇军, 等. 高原脑水肿发病机制及防治研究进展[J]. 人民军医, 2020, 63(4): 343-346, 357. DOI: CNKI:SUN:RMJZ.0.2020-04-013

LIAN G F, LI J, LUO Y J, et al . Research progress on the pathogenesis and prevention of high altitude cerebral edema[J ] . People Mil Surg, 2020, 63(4): 343-346, 357. DOI: CNKI:SUN:RMJZ.0.2020-04-013

FIORE D C, HALL S, SHOJA P. Altitude illness: risk factors, prevention, presentation, and treatment[J]. Am Fam Physician, 2010, 82(9): 1103-1110. [PubMed]

SYDYKOV A, MAMAZHAKYPOV A, MARIPOV A, et al . Pulmonary hypertension in acute and chronic high altitude maladaptation disorders[J ] . Int J Environ Res Public Health, 2021, 18(4): 1692. DOI: 10.3390/ijerph18041692.

贾守宁, 孙梦茹, 马春花, 等. 红景天苷对高原红细胞增多症大鼠红细胞膜结构和功能的影响[J]. 中草药, 2020, 51(15): 3960-3967. DOI: 10.7501/j.issn.02532670.2020.15.015.

JIA S N, SUN M R, MA C H, et al . Effects of salidroside on structure and function of erythrocyte membrane in high altitude polycythemia rats[J ] . Chin Tradit Herb Drugs, 2020, 51(15): 3960-3967. DOI: 10.7501/j.issn.0253-2670.2020.15.015.

LUKS A M, SWENSON E R, BÄRTSCH P. Acute high-altitude sickness[J]. Eur Respir Rev, 2017, 26(143): 160096. DOI: 10.1183/16000617.0096-2016.

PRASAD J, BAITHARU I, SHARMA A K, et al . Quercetin reverses hypobaric hypoxia-induced hippocampal neurodegeneration and improves memory function in the rat[J ] . High Alt Med Biol, 2013, 14(4): 383-394. DOI: 10.1089/ham.2013.1014.

王黎, 史清海, 胡科妍, 等. 优化及复氧对急进高原缺氧大鼠认知功能障碍的改善作用[J]. 华南国防医学杂志, 2018, 32(1): 5-7, 41. DOI: 10.13730/j.issn.1009-2595.2018.01.002.

WANG L, SHI Q H, HU K Y, et al . Improvement of optimization and reoxygenation on cognitive dysfunction in plateau hypoxia rats[J ] . Mil Med J South China, 2018, 32(1): 5-7, 41. DOI: 10.13730/j.issn.1009-2595.2018.01.002.

陈甄, 张广波, 周迪, 等. 急性高原低氧环境对不同情绪状态脑电功率的影响[J]. 中国应用生理学杂志, 2020, 36(6): 556-561. DOI: 10.12047/j.cjap.5978.2020.117.

CHEN Z, ZHANG G B, ZHOU D, et al . Effects of acute high altitude hypoxia on EEG power in different emotional states[J ] . Chin J Appl Physiol, 2020, 36(6): 556-561. DOI: 10.12047/j.cjap.5978.2020.117.

田奡文. 孤啡肽对新物体识别记忆的调节作用及机制研究[D]. 南昌: 南昌大学, 2019.

TIAN A W. The role ofnociceptin in novel object recognition memory and the undelying mechanisms[D]. Nanchang: Nanchang University, 2019.

MCEWEN B S, EILAND L, HUNTER R G, et al . Stress and anxiety: structural plasticity and epigenetic regulation as a consequence of stress[J ] . Neuropharmacology, 2012, 62(1): 3-12. DOI: 10.1016/j.neuropharm.2011.07.014.

HERMAN J P, FLAK J, JANKORD R. Chronic stress plasticity in the hypothalamicparaventricular nucleus[J]. Prog Brain Res, 2008, 170: 353-364. DOI: 10.1016/S0079-6123(08)00429-9.

阮俊勇, 雷涛, 董旭, 等. 急性低压低氧环境对脑功能及其结构影响的研究进展[J]. 中华物理医学与康复杂志, 2020, 42(9): 858-860. DOI: 10.3760/cma.j.issn.0254-1424.2020.09.022.

RUAN J Y, LEI T, DONG X, et al . Research progress on the effects of acute low pressure and hypoxia environment on brain function and structure[J ] . Chin J Phys Med Rehabil, 2020, 42(9): 858-860. DOI: 10.3760/cma.j.issn.0254-1424.2020.09.022.

霍军丽, 董秋峰, 王国霞. 丹参酮ⅡA对高原缺氧大鼠认知功能障碍的影响[J]. 神经解剖学杂志, 2019, 35(5): 505-509. DOI: 10.16557/j.cnki.1000-7547.2019.05.008.

HUO J L, DONG Q F, WANG G X. The effects of Tanshinone ⅡA on high altitude hypoxia-induced cognitive deficits in rats[J]. Chin J Neuroanat, 2019, 35(5): 505-509. DOI: 10.16557/j.cnki.1000-7547.2019.05.008.

蔡明春, 黄庆愿, 徐刚, 等. 间断性高原低氧-复氧对大鼠心脏的影响[J]. 中国循证心血管医学杂志, 2019, 11 (11): 1315-1318. DOI: CNKI:SUN:PZXX.0.2019-11-010

CAI M C, HUANG Q Y, XU G, et al . Influence of intermittent plateau hypoxia/reoxygenation on rat heart[J ] . Chin J Evid Based Cardiovasc Med, 2019, 11(11): 1315-1318. DOI: CNKI:SUN:PZXX.0.2019-11-010

胡晓兰, 邱水凤, 梅如焕, 等. 红景天注射液对油酸诱导兔急性肺损伤的防治作用[J]. 中草药, 2008(11): 1706-1709. DOI: 10.3321/j.issn:0253-2670.2008.11.035.

HU X L, QIU S F, MEI R H, et al . Preventive and therapeutic effects of Hongjingtian injection on acute lung injury induced by oleic acid in rabbits[J ] . Chin Tradit Herb Drugs, 2008(11): 1706-1709. DOI: 10.3321/j.issn:0253-2670.2008.11.035.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Effects of benefit finding training on emotion, resilience and post-traumatic growth in college freshmen

Survey of mental health status of first-line healthcare workers in designated hospitals for COVID-19 in Wuhan

Survey of anxiety and depressive symptoms and analysis of their risks factors among individuals quarantined for COVID-19

Poor sleep quality, anxiety and depression are associated with an increased suicide risk in patients with coronavirus disease 2019

Related Author

Li PENG

Min LI

Wei HE

Zonghua WANG

Lei WANG

Xin DU

Qin LI

Yulu CHEN

Related Institution

Department of Military Psychology, College of Psychology, Army Medical University (Third Military Medical University)

Department of Gastroenterology, Second Affiliated Hospital, Army Medical University (Third Military Medical University)

Department of Clinical Nursing, School of Nursing, Army Medical University (Third Military Medical University)

Department of Nursing, Second Affiliated Hospital, Army Medical University (Third Military Medical University)

Medical Center of Hematology, Second Affiliated Hospital, Army Medical University (Third Military Medical University)

⁰