Genome-wide differential DNA methylation in hippocampus of rats after benzo(a)pyrene exposure

Qiang TAN; Jing WANG; Chunlin LI; Ping TANG; Tao KUANG; Qiang HUANG; Chengzhi CHEN; Xuejun JIANG; Shuqun CHENG; Baijie TU; Yinyin XIA

doi:10.16016/j.1000-5404.201909139

您当前的位置：

首页 >

文章列表页 >

Genome-wide differential DNA methylation in hippocampus of rats after benzo(a)pyrene exposure

Basic Medicine | 更新时间：2026-01-09

- Genome-wide differential DNA methylation in hippocampus of rats after benzo(a)pyrene exposure
- Journal of Third Military Medical University Vol. 42, Issue 4, Pages: 359-366(2020)
- 作者机构：
  
  1.400016 重庆，重庆医科大学公共卫生与管理学院，医学与社会发展研究中心，健康领域社会风险预测治理协同创新中心
  2.611430 成都，四川省成都市新津县疾病预防控制中心
  3.400010 重庆，重庆医科大学附属第二医院预防保健科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81502777);the General Program of National Natural Science Foundation of China(81372957)
- DOI：10.16016/j.1000-5404.201909139
  CLC： R322.81; R394.1; R994.6
- Received：18 September 2019，
  
  Revised：2019-12-10，
  
  Published：28 February 2020
- 稿件说明：
移动端阅览
Qiang TAN, Jing WANG, Chunlin LI, et al. Genome-wide differential DNA methylation in hippocampus of rats after benzo(a)pyrene exposure[J]. Journal of Third Military Medical University, 2020, 42(4): 359-366.
DOI：

Qiang TAN, Jing WANG, Chunlin LI, et al. Genome-wide differential DNA methylation in hippocampus of rats after benzo(a)pyrene exposure[J]. Journal of Third Military Medical University, 2020, 42(4): 359-366. DOI： 10.16016/j.1000-5404.201909139.

摘要

目的

研究苯并芘暴露大鼠海马组织的DNA甲基化差异，探讨苯并芘对海马功能损伤的机制。

方法

将大鼠分为对照组和苯并芘染毒组，每组10只；染毒结束后，采用Morris水迷宫检测大鼠的空间记忆学习能力，随后对大鼠海马进行HE染色与简化表观亚硫酸氢盐测序法(reduced representation bisulfite sequencing

RRBS)测序，对测序结果进行GO和KEGG分析，用qRT-P

CR检测

Tnr

基因与

Pla

基因mRNA的表达。

结果

Morris水迷宫与HE染色发现苯并芘暴露导致了大鼠空间学习记忆能力的障碍与海马组织损伤；RRBS测序后检测到差异性甲基化区域32个，GO分析富集到871条GO条目，KEGG分析得到52条通路，其中145条GO条目和11条通路显著富集(

0.05)，苯并芘染毒组与对照组相比，

Tnr

基因相对表达量减少，而

Pla

基因相对表达量增加(

0.05)。

结论

与未染毒的大鼠相比，苯并芘染毒后大鼠海马组织存在一定数量的甲基化差异位点，这些甲基化差异位点可能对研究苯并芘导致海马损伤的机制具有重要指导意义。

Abstract

Objective

To study the differential DNA methylation in the hippocampus of rats exposed to benzo(a)pyrene and explore the mechanism of benzo(a)pyrene-induced functional impairment of the hippocampus.

Methods

Twenty male SD rats (3 weeks old) were randomly divided into control group and benzo(a)pyrene exposure group (

=10)

and in the latter group

the rats were exposed to benzo(a)pyrene delivered

via

gavage on a daily basis for 7 consecutive weeks. After the exposure

Morris water maze test was performed to assess the changes in the spatial memory and learning ability of rats; the brain tissues were dissected for morphological examination of the hippocampal neurons with HE staining. Reduced representation bisulfite sequencing (RRBS) of the genomic DNA from the hippocampus was performed

followed by GO and KEGG analyses of the sequencing data; qRT-PCR was used to detect the expression levels of

Tnr

and

Pla

mRNAs.

Results

Morris water maze test and HE staining showed that exposure to benzo(a)pyrene resulted in obvious impairment of the spatial learning and memory abilities and caused hippocampal injuries in rats. DNA methylation sequencing identified 32 differentially methylated regions; GO analysis enriched 871 GO items and

KEGG analysis obtained 52 pathways

of which 145 GO items and 11 pathways were significantly enriched (

0.05). Compared with the control rats

the benzo(a)pyrene-exposed rats showed significantly decreased

Tnr

mRNA expression and increased

Pla

mRNA expressions in the hippocampus(

0.05).

Conclusion

A number of differentially methylated sites occur in the genomic DNA in rat hippocampus following benzo(a)pyrene exposure

and these sites may provide important clues in exploring the mechanism of benzo(a)pyrene-induced hippocampal injury.

关键词

Keywords

references

KIM K H, JAHAN S A, KABIR E, et al . A review of airborne polycyclic aromatic hydrocarbons (PAHs) and their human healtheffects[J ] . Environ Int, 2013, 60: 71-80. DOI: 10.1016/j.envint.2013.07.019.

代文娟, 黄海燕, 胡恭华.苯并芘致肺癌的研究进展[J].毒理学杂志, 2018, 32(6): 489-493. DOI: 10.16421/j.cnki.1002-3127.2018.06.014.

DAI W J, HUANG H Y, HU G H. Research progress of lung cancer caused bybenzopyrene[J]. J Toxicol, 2018, 32(6): 489-493. DOI: 10.16421/j.cnki.1002-3127.2018.06.014.

CHENG S Q, XIA YY, HE J L, et al . Neurotoxic effect of subacute benzo(a)pyrene exposure on gene and protein expression in Sprague-Dawley rats[J ] . Environ Toxicol Pharmacol, 2013, 36(2): 648-658. DOI: 10.1016/j.etap.2013.06.008.

曹家雪, 张红平, 杜立新.环境因素对DNA甲基化的影响[J].遗传, 2013, 35(7): 839-846.

CAO J X, ZHANG H P, DU L X. Influence of environmental factors on DNAmethylation[J]. Hereditas, 2013, 35(7): 839-846.

金灵, 张元珍.孕期外源物暴露致DNA甲基化异常与发育源性疾病的关系研究[J].中华生殖与避孕杂志, 2018, 38(6): 521-525. DOI: 10.3760/cma.j.issn.2096-2916.2018.06.017.

JIN L, ZHANG Y Z. Relation of abnormal DNA methylation induced by prenatalxenobiotics exposure and the development origins of disease[J]. Chin J Reprod Contracept, 2018, 38(6): 521-525. DOI: 10.3760/cma.j.issn.2096-2916.2018.06.017.

鞠恩霞, 李红, 龙长权, 等.基于神经成像技术的青少年大脑发育研究[J].心理科学进展, 2010, 18(6): 907-913.

JU E X, LI H, LONG C Q, et al . A neuroimaging-based review of the teen braindevelopment[J ] . Adv Psychol Sci, 2010, 18(6): 907-913.

LI C L, WANG J, SU Q P, et al . Postnatalsubacute benzo(a)pyrene exposure caused neurobehavioral impairment and metabolomic changes of cerebellum in the early adulthood period of sprague-dawley rats[J ] . Neurotox Res, 2018, 33(4): 812-823. DOI: 10.1007/s12640-017-9832-8.

凡时财, 李承哲, 裴云飞.人类基因组DNA甲基化数据分析的研究现状[J].中国科学:生命科学, 2015, 45(5): 450-459. DOI: 10.1360/N052015-00009.

FAN S C, LI C Z, PEI Y F. DNAmethylome data analysis in human genome[J]. Sci Sin Vitae, 2015, 45(5): 450-459. DOI: 10.1360/N052015-00009.

唐倩, 夏茵茵, 程淑群, 等.苯并芘对大鼠记忆及谷氨酸盐受体基因表达影响[J].中国公共卫生, 2011, 27(7): 902-903. DOI: 10.11847/zgggws2011-27-07-39.

TANG Q, XIA Y Y, CHENG S Q, et al . Effect of benzo(a) pyrene on memory and expression of glutamate receptor mRNA in rat[J ] . Chin J Public Heal, 2011, 27(7): 902-903. DOI: 10.11847/zgggws2011-27-07-39.

李宁, 刘紫阳, 詹向红, 等.长期负性情绪应激对D-gal大鼠认知功能及海马NR2B基因甲基化表达的影响[J].中国中西医结合杂志, 2019, 39(6): 702-707. DOI: 10.7661/j.cjim.20190123.126.

LI N, LIU Z Y, ZHAN X H, et al . Effects of long-term negative emotional stress on cognitive function and methylation of NR2B gene in Hippocampus of D-gal rats[J ] . Chin J Integr Tradit West Med, 2019, 39(6): 702-707. DOI: 10.7661/j.cjim.20190123.126.

陈旭涛, 万卓, 韦梦影, 等.大鼠BMSCs与ADSCs全基因组DNA甲基化差异分析[J].实用口腔医学杂志, 2019, 35(2): 170-175. DOI: 10.3969/j.issn.1001-3733.2019.02.002.

CHEN X T, WAN Z, WEI M Y, et al . Comparison of the DNA methylation in a genome wide between BMSCs and ADSCs[J ] . J Pract Stomatol, 2019, 35(2): 170-175. DOI: 10.3969/j.issn.1001-3733.2019.02.002.

WANG J, LI C L, TU B J, et al . Integrated epigenetics, transcriptomics, and metabolomics to analyze the mechanisms of benzo[a ] pyrene neurotoxicity in the Hippocampus[J ] . Toxicol Sci, 2018, 166(1): 65-81. DOI: 10.1093/toxsci/kfy192.

AN L, LI Z Y, YANG Z, et al . Cognitive deficits induced by melamine inrats[J ] . Toxicol Lett, 2011, 206(3): 276-280. DOI: 10.1016/j.toxlet.2011.08.009.

YANG K, CHEN C Z, CHENG S Q, et al . Effects ofbenzo(a)pyrene exposure on the ATPase activity and calcium concentration in the hippocampus of neonatal rats[J ] . Int J Occup Med Environ Health, 2017, 30(2): 203-211. DOI: 10.13075/ijomeh.1896.00744.

王一夫, 刘爽. MAPKs信号通路与阿尔兹海默病的研究进展[J].世界中医药, 2016, 11(9): 1929-1931. DOI: 10.3969/j.issn.1673-7202.2016.09.073.

WANG Y F, LIU S. The research progress of Alzheimer's disease and MAPKs signaling pathways[J]. World Chin Med, 2016, 11(9): 1929-1931. DOI: 10.3969/j.issn.1673-7202.2016.09.073.

张盼盼, 韩晓庆, 李琳, 等.间歇低氧大鼠细胞外信号调节激酶与认知功能变化[J].中国神经精神疾病杂志, 2014, 40(9): 517-521. DOI: 10.3936/j.issn.1002-0152.2014.09.002.

ZHANG P P, HAN X Q, LI L, et al . The effect of intermittent hypoxia on hippocampal ERK signaling and cognitive function in rats[J ] . Chin J Nerv Ment Dis, 2014, 40(9): 517-521. DOI: 10.3936/j.issn.1002-0152.2014.09.002.

FELD M, DIMANT B, DELORENZI A, et al . Phosphorylation of extra-nuclear ERK/MAPK is required for long-term memory consolidation in the crab Chasmagnathus[J ] . Behav Brain Res, 2005, 158(2): 251-261. DOI: 10.1016/j.bbr.2004.09.005.

[PARK H J, KWON H, LEE J H, et al .β-amyrin ameliorates alzheimer's disease-like aberrant synaptic plasticity in the mouse hippocampus[J ] . Biomol Ther (Seoul), 2019 Jul 30. DOI: 10.4062/biomolther.2019.024 http://dx.doi.org/10.4062/biomolther.2019.024 ..

黄文辉, 廖红, 牛蕤, 等.细胞外基质分子Tenascin-R的研究进展[J].中国药科大学学报, 2007, 38(4): 375-379. DOI: 10.3321/j.issn: 1000-5048.2007.04.020.

HUANG W H, LIAO H, NIU R, et al . Progress in extracellular matrix molecule tenascin-R[J ] . J China Pharm Univ, 2007, 38(4): 375-379. DOI: 10.3321/j.issn: 1000-5048.2007.04.020.

SAGHATELYAN A K, DITYATEV A, SCHMIDT S, et al . Reducedperisomatic inhibition, increased excitatory transmission, and impaired long-term potentiation in mice deficient for the extracellular matrix glycoprotein tenascin-R[J ] . Mol Cell Neurosci, 2001, 17(1): 226-240. DOI: 10.1006/mcne.2000.0922.

杨武, 郭薇, 黄春洪.分泌型磷脂酶A2亚家族:结构与功能[J].中国生物化学与分子生物学报, 2013, 29(10): 932-940. DOI: 10.13865/j.cnki.cjbmb.2013.10.006.

YANG W, GUO W, HUANG C H. The subfamily of secretory phospholipase A2: structure and functions[J]. Chin J Biochem Mol Biol, 2013, 29(10): 932-940. DOI: 10.13865/j.cnki.cjbmb.2013.10.006.

LEE J C, SIMONYI A, SUN A Y, et al . Phospholipases A2 and neural membrane dynamics: implications for Alzheimer's disease[J ] . J Neurochem, 2011, 116(5): 813-819. DOI: 10.1111/j.1471-4159.2010.07033.x.

沈圣, 屈彦纯, 张军.下一代测序技术在表观遗传学研究中的重要应用及进展[J].遗传, 2014, 36(3): 256-275. DOI: 10.3724/SP.J.1005.2014.0256.

SHEN S, QU Y C, ZHANG J. The application of next generation sequencing on epigeneticstudy[J]. Hereditas, 2014, 36(3): 256-275. DOI: 10.3724/SP.J.1005.2014.0256.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Effect of dexmedetomidine on sevoflurane-induced endoplasmic reticulum stress in hippocampus of neonatal rats

Effects of Toll-like receptor 4 inhibitor on hypoxic-ischemic hippocampal neurons and dendritic spines in neonatal rats

Changes of hydrogen sulfide/cystathionine-β-synthase system in hippocampus of heroin-addictive rats

Effect of ketamine in expressions of NR2A-2C receptor subunits in hippocampal dentate gyrus of neonatal rats

Effects of clesmatine on myelination and neuronal activity during sleep in the hippocampus of adult APP/PS1 mice

Related Author

白鹏祖

张利亮

张海盛

姚泽宇

朱杏

唐振

向希盈

孙艳燕

Related Institution

Department of Physiology, College of Basic Medical Sciences， Army Medical University （Third Military Medical University）

Experimental Center of Basic Medicine, College of Basic Medical Sciences， Army Medical University （Third Military Medical University）

Department of Neurobiology， College of Basic Medical Sciences， Army Medical University （Third Military Medical University）

Sports Medicine Center， First Affiliated Hospital， Army Medical University （Third Military Medical University）

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

⁰