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Article(id=1240413933698338827, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240413921266429979, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202503180, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1741708800000, receivedDateStr=2025-03-12, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773667327569, onlineDateStr=2026-03-16, pubDate=1754755200000, pubDateStr=2025-08-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773667327569, onlineIssueDateStr=2026-03-16, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773667327569, creator=13701087609, updateTime=1773667327569, updator=13701087609, issue=Issue{id=1240413921266429979, tenantId=1146029695717560320, journalId=1227665162245664772, year='2025', volume='52', issue='15', pageStart='2689', pageEnd='2880', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1773667324606, creator=13701087609, updateTime=1773667356299, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1240414054267802325, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240413921266429979, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1240414054267802326, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1240413921266429979, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=2848, endPage=2853, ext={EN=ArticleExt(id=1240413933991940140, articleId=1240413933698338827, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Effects of extreme light conditions on m6A methylation regulators in mouse brain regions, columnId=1228016572065837304, journalTitle=Modern Preventive Medicine, columnName=Experimental Technology and Applications, runingTitle=null, highlight=null, articleAbstract=
Objective

To investigate whether extreme light conditions alter the expression of RNA m6A methylation regulators in brain regions during anxiety- and depression-like behaviors in mice.

Methods

A total of 48 male C57BL/6J mice were randomly divided into control, constant light, and constant dark groups (n=8 per group) for 2- or 4-week interventions.Behavioral tests assessed anxiety- and depression-like behaviors. After completion of these assessments, the medial prefrontal cortex, hypothalamus, amygdala, and ventral hippocampus were collected for qRT-PCR analysis of m6A methyltransferases and reader proteins. Differences between groups were determined using one-way ANOVA with multiple comparisons.

Results

Compared with the control group, after 2 weeks, constant dark exposure induced significant anxiety- and depression-like behaviors (P<0.01), while constant light showed no effect. After 4 weeks, both extreme light conditions caused behavioral abnormalities (P<0.01). Compared with the control group, qRT-PCR revealed that 2-week constant dark exposure significantly altered m6A regulators: increased Mettl3 in medial prefrontal cortex (P<0.05); decreased Mettl3 and YthdF1 in hypothalamus (P<0.05); increased FTO and ALKBH5 but decreased YthdC1 in ventral hippocampus (P<0.05); and increased ALKBH5/YthdC2 but decreased YthdC1 in amygdala (P<0.05).

Conclusion

Constant dark exposure more readily induces anxiety- and depression-like behaviors than constant light, and extreme light conditions modify the expression profile of RNA m6A methylation regulators in emotion-related brain regions.

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目的

本实验旨在探究极端光照诱导小鼠焦虑抑郁样行为过程中是否会改变脑区RNA m6A甲基化调控因子的表达。

方法

48只C57BL6J雄性小鼠随机分为对照组、持续光照组、持续黑暗组，每组8只，建立模型时长为2周、4周。通过行为学实验评估小鼠的焦虑抑郁样行为改变。行为学检测结束后，分别取小鼠内侧前额叶皮层、下丘脑、杏仁核、腹侧海马，通过qRT-PCR检测RNA m6A甲基化酶和阅读蛋白的水平。统计学方法采用单因素方差分析以及多重比较确定组间是否存在统计学差异。

结果

与对照组对比后发现，在为期2周的极端光照环境暴露后，持续黑暗组小鼠出现了焦虑抑郁样行为（P<0.01），而持续光照小鼠无显著变化；4周的极端光照环境暴露后，持续黑暗组和持续光照组小鼠均表现出明显的焦虑抑郁样行为（P<0.01）。qRT-PCR结果显示，与对照组相比，持续2周处于黑暗环境的小鼠，各情绪调控脑区的m6A甲基化调控因子出现了显著变化，主要包括，与对照组比较，内侧前额叶皮层的Mettl3显著升高（P<0.05）；下丘脑Mettl3、YthdF1显著降低（P<0.05）；腹侧海马FTO、ALKBH5显著升高，YthdC1显著降低（P<0.05）；杏仁核ALKBH5、YthdC2显著升高，YthdC1显著下降（P<0.05）。

结论

持续黑暗相较于持续光照会更容易诱导小鼠出现焦虑抑郁样行为，并且，极端光环境会改变小鼠RNA m6A甲基化调控因子的表达。

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张艳淑，E-mail: ；
钱令嘉，E-mail:；
, copyrightStatement=本刊刊出的所有文章不代表中华预防医学会和本刊编委会的观点，除非特别声明。, copyrightOwner=中华预防医学会和四川大学华西公共卫生学院, extLink=null, articleAbsUrl=null, sourceXml=CWobvVACajYsp97usKBx7g==, magXml=2wUN+BQ1fMtJ7eXwIqS7Cg==, pdfUrl=null, pdf=eMbiD/oCWhEsXi4Vj/1TRA==, pdfFileSize=1164338, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=A8GE7aprL1AAEn9szFsZsg==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=DMnPv6AF3x4nS1QVy5fsDw==, mapNumber=null, authorCompany=null, fund=null, authors=

张艳淑与钱令嘉为共同通信作者

刘薇薇（1999—），女，硕士在读，研究方向:卫生毒理学

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刘薇薇（1999—），女，硕士在读，研究方向:卫生毒理学

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刘薇薇（1999—），女，硕士在读，研究方向:卫生毒理学

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注：A糖水偏好试验；B～C高架十字迷宫统计图；与对照组比较，**P<0.01，ns为P>0.05；单因素方差分析。

, figureFileSmall=vC8d0K/Y7pZDtEMtxv/I5Q==, figureFileBig=qcR+j/MAA9mIPexiMPbKaw==, tableContent=null), ArticleFig(id=1240424361505649602, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413933698338827, language=EN, label=Figure 2, caption=Behavioral test of mice exposed to extreme light environment for four weeks (n=8), figureFileSmall=8NheADpjZ1Q2wzvJ86tldw==, figureFileBig=96vWE1wkitrZoVcil2sKUQ==, tableContent=null), ArticleFig(id=1240424361606312902, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413933698338827, language=CN, label=图2, caption=4周极端光环境暴露小鼠行为学检测(n=8)

注：A糖水偏好实验；B～C高架十字迷宫统计图；与对照组比较，**P<0.01，单因素方差分析。

, figureFileSmall=8NheADpjZ1Q2wzvJ86tldw==, figureFileBig=96vWE1wkitrZoVcil2sKUQ==, tableContent=null), ArticleFig(id=1240424361719559113, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413933698338827, language=EN, label=Figure 3, caption=mRNA expression of methylation regulators in the medial prefrontal cortex of mice (n=3), figureFileSmall=XwJZOUMnJx1UsKym+QwiJg==, figureFileBig=6c0QcLUnS7Tz3C98Ix87iw==, tableContent=null), ArticleFig(id=1240424361836999627, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413933698338827, language=CN, label=图3, caption=小鼠内侧前额叶皮层甲基化调控因子mRNA表达(n=3)

注：与对照组比较，*P<0.05，单因素方差分析。

, figureFileSmall=XwJZOUMnJx1UsKym+QwiJg==, figureFileBig=6c0QcLUnS7Tz3C98Ix87iw==, tableContent=null), ArticleFig(id=1240424361933468623, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413933698338827, language=EN, label=Figure 4, caption=mRNA expression of methylation regulators in mouse hypothalamus (n=3), figureFileSmall=7x2vPddVq9w2VlTWdUH0VQ==, figureFileBig=+JJGSHR1UHlH9LHKQWEoGg==, tableContent=null), ArticleFig(id=1240424362025743317, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413933698338827, language=CN, label=图4, caption=小鼠下丘脑甲基化调控因子mRNA表达(n=3)

注：与对照组比较，*P<0.05，单因素方差分析。

, figureFileSmall=7x2vPddVq9w2VlTWdUH0VQ==, figureFileBig=+JJGSHR1UHlH9LHKQWEoGg==, tableContent=null), ArticleFig(id=1240424362147378138, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413933698338827, language=EN, label=Figure 5, caption=mRNA expression of methylation regulators in ventral hippocampus of mice (n=3), figureFileSmall=6jXYDIqTIZzYR0a+eoowQg==, figureFileBig=8AYbRb3pSjmzq09oYFP+ZA==, tableContent=null), ArticleFig(id=1240424362235458524, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413933698338827, language=CN, label=图5, caption=小鼠腹侧海马甲基化调控因子mRNA表达(n=3)

注：与对照组比较，*P<0.05，单因素方差分析。

, figureFileSmall=6jXYDIqTIZzYR0a+eoowQg==, figureFileBig=8AYbRb3pSjmzq09oYFP+ZA==, tableContent=null), ArticleFig(id=1240424362327733216, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413933698338827, language=EN, label=Figure 6, caption=mRNA expression of methylation regulators in amygdala of mice (n=3), figureFileSmall=j4vuoc9UijNpY3bbonH9rw==, figureFileBig=e3H+oqn/fNyss1pxMB2KLg==, tableContent=null), ArticleFig(id=1240424362415813602, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413933698338827, language=CN, label=图6, caption=小鼠杏仁核甲基化调控因子mRNA表达(n=3)

注：与对照组比较，**P<0.01, *P<0.05，单因素方差分析。

, figureFileSmall=j4vuoc9UijNpY3bbonH9rw==, figureFileBig=e3H+oqn/fNyss1pxMB2KLg==, tableContent=null), ArticleFig(id=1240424362508088293, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413933698338827, language=EN, label=Table 1, caption=

Primer sequence

, figureFileSmall=null, figureFileBig=null, tableContent=
基因名称上游引物（5’→3’）下游引物（5’→3’）
METTL3CTGGGCACTTGGATTTAAGGAATGAGAGGTGGTGTAGCAACTT
METTL14CTGAGAGTGCGGATAGCATTGGAGCAGATGTATCATAGGAAGCC
YTHDF1ACAGTTACCCCTCGATGAGTGGGTAGTGAGATACGGGATGGGA
YTHDC1GTCCACATTGCCTGTAAATGAGAGGAAGCACCCAGTGTATAGGA
YTHDC2ACCGACTAAGTCAATCTCTTGGTAGGCTCCTAACAGCATGTTTTG
WTAPGAACCTCTTCCTAAAAAGGTCCGTTAACTCATCCCGTGCCATAAC
FTOTCCTCAGAAGATGCCCTACTTGCCCAACATTACCCAGCATGAAA
ALKBH5CGCGGTCATCAACGACTACCATGGGCTTGAACTGGAACTTG
β-ACTINGTGGATCAGCAAGCAGGAGTGAGGTATTCGCACCAGAGGA
), ArticleFig(id=1240424362591974376, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1240413933698338827, language=CN, label=表1, caption=

引物序列

, figureFileSmall=null, figureFileBig=null, tableContent=
基因名称上游引物（5’→3’）下游引物（5’→3’）
METTL3CTGGGCACTTGGATTTAAGGAATGAGAGGTGGTGTAGCAACTT
METTL14CTGAGAGTGCGGATAGCATTGGAGCAGATGTATCATAGGAAGCC
YTHDF1ACAGTTACCCCTCGATGAGTGGGTAGTGAGATACGGGATGGGA
YTHDC1GTCCACATTGCCTGTAAATGAGAGGAAGCACCCAGTGTATAGGA
YTHDC2ACCGACTAAGTCAATCTCTTGGTAGGCTCCTAACAGCATGTTTTG
WTAPGAACCTCTTCCTAAAAAGGTCCGTTAACTCATCCCGTGCCATAAC
FTOTCCTCAGAAGATGCCCTACTTGCCCAACATTACCCAGCATGAAA
ALKBH5CGCGGTCATCAACGACTACCATGGGCTTGAACTGGAACTTG
β-ACTINGTGGATCAGCAAGCAGGAGTGAGGTATTCGCACCAGAGGA
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极端光照对小鼠脑区m6A甲基化调控因子的影响
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刘薇薇 1 , 王雪 2 , 赵云 2 , 谢方 2 , 孙兆炜 2 , 董华丰 2 , 张士佳 3 , 张艳淑 1 , 钱令嘉 2
现代预防医学 | 实验技术及其应用 2025,52(15): 2848-2853
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现代预防医学 | 实验技术及其应用 2025, 52(15): 2848-2853
极端光照对小鼠脑区m6A甲基化调控因子的影响
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刘薇薇1, 王雪2, 赵云2, 谢方2, 孙兆炜2, 董华丰2, 张士佳3, 张艳淑1 , 钱令嘉2
作者信息
  • 1.华北理工大学公共卫生学院，河北 唐山 063210
  • 2.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
  • 3.安徽医科大学基础医学院

    • 刘薇薇（1999—），女，硕士在读，研究方向:卫生毒理学

通讯作者:

张艳淑，E-mail: ；
钱令嘉，E-mail:；
Effects of extreme light conditions on m6A methylation regulators in mouse brain regions
Wei-wei LIU1, Xue WANG2, Yun ZHAO2, Fang XIE2, Zhao-wei SUN2, Hua-feng DONG2, Shi-jia ZHANG3, Yan-shu ZHANG1 , Ling-jia QIAN2
Affiliations
  • School of Public Health, North China University of Science and Technology, Tangshan, Hebei 063210, China
出版时间: 2025-08-10 doi: 10.20043/j.cnki.MPM.202503180
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摘要
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目的

本实验旨在探究极端光照诱导小鼠焦虑抑郁样行为过程中是否会改变脑区RNA m6A甲基化调控因子的表达。

方法

48只C57BL6J雄性小鼠随机分为对照组、持续光照组、持续黑暗组，每组8只，建立模型时长为2周、4周。通过行为学实验评估小鼠的焦虑抑郁样行为改变。行为学检测结束后，分别取小鼠内侧前额叶皮层、下丘脑、杏仁核、腹侧海马，通过qRT-PCR检测RNA m6A甲基化酶和阅读蛋白的水平。统计学方法采用单因素方差分析以及多重比较确定组间是否存在统计学差异。

结果

与对照组对比后发现，在为期2周的极端光照环境暴露后，持续黑暗组小鼠出现了焦虑抑郁样行为（P<0.01），而持续光照小鼠无显著变化；4周的极端光照环境暴露后，持续黑暗组和持续光照组小鼠均表现出明显的焦虑抑郁样行为（P<0.01）。qRT-PCR结果显示，与对照组相比，持续2周处于黑暗环境的小鼠，各情绪调控脑区的m6A甲基化调控因子出现了显著变化，主要包括，与对照组比较，内侧前额叶皮层的Mettl3显著升高（P<0.05）；下丘脑Mettl3、YthdF1显著降低（P<0.05）；腹侧海马FTO、ALKBH5显著升高，YthdC1显著降低（P<0.05）；杏仁核ALKBH5、YthdC2显著升高，YthdC1显著下降（P<0.05）。

结论

持续黑暗相较于持续光照会更容易诱导小鼠出现焦虑抑郁样行为，并且，极端光环境会改变小鼠RNA m6A甲基化调控因子的表达。

持续黑暗  /  持续光照  /  焦虑  /  抑郁  /  RNA m6A甲基化
Objective

To investigate whether extreme light conditions alter the expression of RNA m6A methylation regulators in brain regions during anxiety- and depression-like behaviors in mice.

Methods

A total of 48 male C57BL/6J mice were randomly divided into control, constant light, and constant dark groups (n=8 per group) for 2- or 4-week interventions.Behavioral tests assessed anxiety- and depression-like behaviors. After completion of these assessments, the medial prefrontal cortex, hypothalamus, amygdala, and ventral hippocampus were collected for qRT-PCR analysis of m6A methyltransferases and reader proteins. Differences between groups were determined using one-way ANOVA with multiple comparisons.

Results

Compared with the control group, after 2 weeks, constant dark exposure induced significant anxiety- and depression-like behaviors (P<0.01), while constant light showed no effect. After 4 weeks, both extreme light conditions caused behavioral abnormalities (P<0.01). Compared with the control group, qRT-PCR revealed that 2-week constant dark exposure significantly altered m6A regulators: increased Mettl3 in medial prefrontal cortex (P<0.05); decreased Mettl3 and YthdF1 in hypothalamus (P<0.05); increased FTO and ALKBH5 but decreased YthdC1 in ventral hippocampus (P<0.05); and increased ALKBH5/YthdC2 but decreased YthdC1 in amygdala (P<0.05).

Conclusion

Constant dark exposure more readily induces anxiety- and depression-like behaviors than constant light, and extreme light conditions modify the expression profile of RNA m6A methylation regulators in emotion-related brain regions.

Constant darkness  /  Constant light  /  Anxiety  /  Depression  /  RNA m6A methylation
刘薇薇, 王雪, 赵云, 谢方, 孙兆炜, 董华丰, 张士佳, 张艳淑, 钱令嘉. 极端光照对小鼠脑区m6A甲基化调控因子的影响. 现代预防医学, 2025 , 52 (15) : 2848 -2853 . DOI: 10.20043/j.cnki.MPM.202503180
Wei-wei LIU, Xue WANG, Yun ZHAO, Fang XIE, Zhao-wei SUN, Hua-feng DONG, Shi-jia ZHANG, Yan-shu ZHANG, Ling-jia QIAN. Effects of extreme light conditions on m6A methylation regulators in mouse brain regions[J]. Modern Preventive Medicine, 2025 , 52 (15) : 2848 -2853 . DOI: 10.20043/j.cnki.MPM.202503180
正文
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在人类感知世界的过程中，光是极为重要的元素，它不仅为视觉提供基础，更深刻地影响着我们的情绪状态[1-3]。日常生活里，人们对光照的体验大多处于相对温和的范围，然而，在一些特殊场景，如极地地区极昼极夜的漫长更迭、矿井等地下作业环境的人造强光或昏暗光照、个体长时间暴露于极端光照环境之下，其情绪往往会产生独特且显著的变化[4-5]。表观遗传学机制，特别是RNA N6-甲基腺苷（N6-methyladenosine，m6A）在环境因素调控基因表达和神经可塑性中发挥着关键作用[6-8]。RNA m6A甲基化修饰水平受到甲基化转移酶、去甲基化酶和甲基化阅读蛋白的共同调节[9]。值得注意的是，光照作为一种重要的环境信号，能够对生物体的生理状态产生显著影响，而这种影响很可能与m6A修饰存在关联[10]。已有文献报道，光照周期的改变会影响动物的行为模式和情绪状态。同时，在动物实验中发现，不同光照条件下，脑内某些基因的表达会发生变化，且这种变化可能与m6A修饰有关。研究表明，对情绪有重要影响的脑区，如海马、杏仁核和前额叶皮层，其RNA m6A甲基化状态的改变与情绪障碍的发生发展密切相关[11-12]。这些生理层面的改变与情绪波动紧密相连。然而，光照究竟如何具体影响不同脑区m6A调控因子的改变，最终导致焦虑抑郁的发生，目前尚不清楚。本研究旨在探讨极端光照模式对不同脑区甲基化酶表达和活性的影响，为由于环境光照诱导情绪相关疾病的创新疗法研发提供启发。
1　材料与方法
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1.1　实验动物
24只雄性C57BL6j小鼠（6周龄，26～32 g），随机分为对照组、持续光照组和持续黑暗组，暴露时长分别为2周和4周。将不同组动物置于同一环境的不同置物架上开展模型构建。对照组保持正常光暗周期（人工照明12 h、黑暗环境12 h）；持续黑暗组，采用遮光布营造24 h黑暗环境；对持续光照组，借助白炽灯维持24 h照明。实验动物购于北京斯贝福生物科技有限公司。伦理：本研究已获得军事医学研究院伦理委员会批准（IACUC-DWZX-2022- 629）
1.2　实验方法
1.2.1　糖水偏好试验
糖水偏好试验用于评估小鼠对奖励的偏好，抑郁状态下小鼠对糖水的偏好会降低。在本实验正式开始之前三天，先将两个相同的水瓶放于笼上使小鼠适应，待小鼠适应后将小鼠单独饲养，并对小鼠进行水食剥夺。将其中一个水瓶灌满纯净水，另一个加入1%蔗糖溶液，并使小鼠饮用三天，每天对调瓶子的位置并每天测量两瓶水的重量并且记录摄入量。糖水偏好值计算为1%蔗糖溶液摄入量相对于总摄入量的百分比，其公式如下所示：糖水偏好=V（1%蔗糖溶液）/[V（1%蔗糖溶液）+V（水）]×100%
1.2.2　高架十字迷宫实验
由一个区域面积为5 cm×5 cm的公共中心平台和四个臂组成，其中两个开臂面积为30 cm×5 cm和两个闭臂体积为30 cm×5 cm×15 cm，该设备距离地面高度为50 cm，设备上方携带摄像机记录小鼠活动轨迹。将小鼠放置于设备中心平台上，使小鼠面向开臂，记录5 min小鼠的运动轨迹。每只小鼠实验完成后使用75%乙醇溶液擦拭设备去除异味。记录小鼠在开臂和闭臂中停留的时间及次数，进入开放臂时间占比=进入开放臂累积时间/（进入开放臂累积时间+进入封闭臂累积时间）×100%；进入开放臂频率占比=进入开放臂累积次数/（进入开放臂累积次数+进入封闭臂累积次数）×100%。
1.2.3　RNA反转录及实时荧光定量聚合酶链反应（qRT-PCR）分析
行为学检测结束后，提取极端光环境暴露2周小鼠的内侧前额叶皮层、下丘脑、腹侧海马和杏仁核组织的RNA，每个脑区随机选取每组的3只小鼠进行检测。根据组织体积加入适量Trizol，每1ml Trizol加入200 μl三氯甲烷、600 μl的异丙醇和75%乙醇，孵育并离心，提取RNA。使用PrimeScriptTM RT Master Mix将总RNA（2 μg）反转录为cDNA。为保持一致性，本实验使用β-肌动蛋白基因作为内参基因，对每个样本的总RNA水平进行标准化。引物序列见表1。
1.2.4　统计学分析
采用GraphPad Prism®9.5.1软件统计，数据以（均数±标准误）表示，多组均数间的差异采用单因素分析比较，检验水准α=0.05。
2　结果
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2.1　持续黑暗更易诱导小鼠焦虑抑郁样行为
在极端光环境暴露2周后，不同类型的极端光照模式下小鼠的行为学检测结果不同。与对照组比较，持续光照组小鼠在行为学检测中未出现差异；持续黑暗组小鼠的蔗糖偏释度显著降低，出现抑郁样行为；高架十字迷宫实验其进入开放臂占比显著降低，表现出焦虑抑郁样行为，见图1。以上结果提示，相较于持续光照，持续黑暗更容易诱导小鼠焦虑抑郁样行为。
2.2　4周极端光照暴露诱导小鼠出现焦虑抑郁行为
4周的极端光照模型下，与对照组比较，持续黑暗组和持续光照组小鼠均出现蔗糖偏释度显著降低，高架十字迷宫实验中进入开放臂占比显著降低，表现出焦虑抑郁样行为。见图2。
2.3　极端光照环境对不同脑区m6A甲基化调控因子的影响
内侧前额叶皮层、下丘脑、杏仁核以及腹侧海马被证实与机体情绪调控密切相关[8-10]，进而提取了极端光环境暴露2周小鼠各脑区的RNA，通过qRT-PCR检测极端光照环境对上述脑区甲基化调控因子的影响。结果发现，在与情绪调控密切相关的四个脑区中，检测到不同调控因子的改变。持续黑暗组小鼠内侧前额叶皮层METTL3显著升高（见图3），下丘脑组织METTL3和YthdF1表达降低（见图4），腹侧海马FTO和ALKBH5的表达升高、YthdC1表达降低（见图5），以及杏仁核ALKBH5表达升高、YthdC1和YthdC2表达降低（见图6）。甲基化酶水平升高可诱导RNA甲基化水平升高，而去甲基化酶水平升高则提示该脑区RNA甲基化水平降低；甲基化阅读蛋白的异常改变会扰乱mRNA的代谢进程，包括剪接、转运以及稳定性，因此特定基因的表达无法精准调控，从而引发下游一系列生理过程的连锁反应。这些结果表明光照缺失可诱导不同脑区的RNA甲基化水平发生不同的变化，这可能与各脑区在情绪调控中的具体作用和分子机制不同有关。
3　讨论
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在现代社会，人类生活的光环境发生了显著改变，这种改变对情绪产生了不容忽视的影响。本研究构建了2周和4周极端光照模型，和前期很多研究结果一致，三周及以上异常光环境暴露都会扰乱小鼠的生物节律，进而影响机体情绪。但是，在本研究中首先建立了极端光环境暴露2周的模型，发现相较于持续光照，持续黑暗的环境更容易诱导小鼠出现焦虑和抑郁样行为。可能在持续光照下，小鼠仍能感知到光线的存在，生物钟可能部分维持其节律性；而在持续黑暗中，小鼠完全失去外界光线的提示，生物节律更容易发生紊乱。
m6A甲基化作为一种广泛存在于真核生物RNA上的修饰方式，在生物的生长发育、疾病发生发展等众多生物学过程中扮演着极为关键的角色[13-14]。在分子机制层面，光环境的改变可能通过影响m6A修饰相关酶的活性来调控甲基化水平[15-16]。如在昼夜节律相关研究中发现，光信号可通过视网膜-下丘脑束传递至视交叉上核，进而调节机体的生物钟。这种生物钟的调节可能会间接影 m6A调控因子的表达或活性，最终导致m6A甲基化水平的改变[17-19]。有研究表明，在睡眠期间长期暴露于蓝光下的大鼠，其外侧缰核中mRNA的m6A修饰水平发生了变化；提示光信号与m6A修饰之间存在某种关联途径[20-21]。同时，光环境的改变与焦虑抑郁等精神障碍之间存在紧密联系；考虑到m6A甲基化修饰在神经系统的发育、情绪改变以及神经退行性疾病中具有重要作用[22]，进而推测脑区的m6A甲基化改变可能在光环境改变引起焦虑抑郁等精神损伤的发生发展中扮演一定角色。例如，有研究发现，海马体的m6A甲基化调控因子受光照影响显著[23]。上海科技大学科研团队2018年的研究发现，光照作为外界刺激，通过影响m6A识别蛋白YTHDF1进而调控小鼠空间学习与记忆能力。还有临床疾病分析表明，在阿尔茨海默病相关脑区，如大脑皮质等，m6A甲基化调控因子可能因光照改变而失衡[24-25]。异常的m6A甲基化调控因子会导致相关基因m6A修饰异常，影响基因表达，最终促进阿尔茨海默病的发展[26-27]。光照对不同脑区m6A甲基化调控因子的影响广泛且复杂，但具体到情绪调节相关脑区的研究还尚少。本研究中，选取四个与情绪调节相关的脑区，观察到持续2周处于黑暗环境的小鼠，其各情绪调控脑区的m6A甲基化调控因子发生了显著变化。和之前研究的结果一致，光环境的改变会影响m6A调控因子的显著变化。这些结果表明，极端黑暗环境会显著干扰小鼠情绪调控脑区的m6A甲基化调控体系，并且，不同脑区的变化因子也不尽相同。以上脑区m6A甲基化调控因子的变化进一步暗示，情绪状态的动态变化与RNA m6A甲基化修饰存在内在关联。然而，本研究也存在一定的局限性。首先，虽然观察到了m6A甲基化调控因子的变化，但具体哪些mRNA受到了m6A修饰的影响以及这些修饰如何调控基因表达和神经功能，仍需要进一步的研究。
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2025年第52卷第15期
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doi: 10.20043/j.cnki.MPM.202503180
  • 接收时间：2025-03-12
  • 首发时间：2026-03-16
  • 出版时间：2025-08-10
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  • 收稿日期：2025-03-12
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    1.华北理工大学公共卫生学院，河北 唐山 063210
    2.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
    3.安徽医科大学基础医学院

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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
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红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
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