Role of microRNAs in the pathogenesis and therapy of post⁃traumatic stress disorder

ZHAO Jinying; LI Yahong; ZHAO Wenyan; ZHOU Yuliang; XU Zhipeng

doi:10.14188/j.1671-8852.2024.0141

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Role of microRNAs in the pathogenesis and therapy of post⁃traumatic stress disorder

更新时间：2026-11-05

- Role of microRNAs in the pathogenesis and therapy of post⁃traumatic stress disorder
- Medical Journal of Wuhan University Vol. 46, Issue 9, Pages: 1224-1230(2025)
- 作者机构：
  
  1.武汉大学中南医院神经心理科湖北武汉 430071
  2.中南民族大学应用心理学系湖北武汉 430074
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2024.0141
  CLC： R749.99
- Received：01 March 2024，
  
  Published：26 September 2025
- 稿件说明：
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赵金映,李亚红,赵文艳等.microRNA在创伤后应激障碍发病机制及治疗中的作用[J].武汉大学学报（医学版）,2025,46(09):1224-1230.

ZHAO Jinying,LI Yahong,ZHAO Wenyan,et al.Role of microRNAs in the pathogenesis and therapy of post⁃traumatic stress disorder[J].Medical Journal of Wuhan University,2025,46(09):1224-1230.
赵金映,李亚红,赵文艳等.microRNA在创伤后应激障碍发病机制及治疗中的作用[J].武汉大学学报（医学版）,2025,46(09):1224-1230. DOI： 10.14188/j.1671-8852.2024.0141.

ZHAO Jinying,LI Yahong,ZHAO Wenyan,et al.Role of microRNAs in the pathogenesis and therapy of post⁃traumatic stress disorder[J].Medical Journal of Wuhan University,2025,46(09):1224-1230. DOI： 10.14188/j.1671-8852.2024.0141.

摘要

创伤后应激障碍(PTSD)在人群中的患病率约为4%~8%，其治疗方法多样，但都难以取得令人满意的长期效果。MicroRNAs(miRs)失调可能是PTSD发病机制中观察到的众多分子变化的基础，故其下游基因有希望成为PTSD的治疗靶点。本文介绍了miRs在PTSD相关发病机制——杏仁核⁃海马⁃前额叶皮质回路和下丘脑⁃垂体⁃肾上腺轴中的作用；总结了miRs在改善PTSD相关焦虑抑郁样行为及靶向基因治疗中的最新证据；并指出了目前相关研究的局限性，旨在为未来miRNA在PTSD中的应用提供新的可能。

Abstract

The incidence rate of post⁃traumatic stress disorder (PTSD) in the general population ranges from 4% to 8%. Despite the increasing diversification of treatment methods

achieving satisfactory long⁃term effects remains challenging. MicroRNAs (miRNAs

miRs) may underlie many molecular changes observed in PTSD pathogenesis

making their downstream genes potential targets for PTSD treatment. This review introduces the role of miRNAs in the pathogenesis of PTSD

specifically within the amygdala⁃hippocampus⁃prefrontal cortex circuit and the hypothalamicpituitary⁃adrenal axis

summarizes the latest evidence on the role of miRNA in ameliorating PTSD related anxiety and depression⁃like behaviors and their potential in targeted gene therapy

and highlights current limitations in related research

aiming to provide new possibilities for future applications of miRNA in PTSD.

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references

刘斌 , 陈晨 , 宋磊 , 等 . 创伤后应激障碍物理治疗潜在脑区靶点的研究进展 [J ] . 空军军医大学学报 , 2023 , 44 ( 11 ): 1118 ⁃ 1122,1127 .

LIU B , CHEN C , SONG L , et al . Research progress on potential brain targets of physical therapy for post⁃traumatic stress disorder [J ] . Journal of Air Force Medical University , 2023 , 44 ( 11 ): 1118 ⁃ 1122,1127 .

RAHMAN S , ZAMMIT S , DALMAN C , et al . Epidemiology of posttraumatic stress disorder: A prospective cohort study based on multiple nationwide Swedish registers of 4.6 million people [J ] . Eur Psychiatry , 2022 , 65 ( 1 ): e60 .

AL JOWF G I , AHMED Z T , REIJNDERS R A , et al . To predict, prevent, and manage post⁃traumatic stress disorder (PTSD): A review of pathophysiology, treatment, and biomarkers [J ] . Int J Mol Sci , 2023 , 24 ( 6 ): 5238 .

IPSER J , SEEDAT S , STEIN D J . Pharmacotherapy for post⁃traumatic stress disorder–A systematic review and meta⁃analysis [J ] . S Afr N Med J , 2006 , 96 ( 10 ): 1088 ⁃ 1096 .

刘阳 , 宁武凤 , 胡茂荣 . 创伤后应激障碍发病机制研究进展 [J ] . 国际精神病学杂志 , 2020 , 47 ( 3 ): 425 ⁃ 428 .

LIU Y , NING W F , HU M R . Research progress on pathogenesis of post⁃traumatic stress disorder [J ] . J Int Psychiatry , 2020 , 47 ( 3 ): 425 ⁃ 428 .

GUPTA S , GULERIA R S , SZABO Y Z . MicroRNAs as biomarker and novel therapeutic target for posttraumatic stress disorder in Veterans [J ] . Psychiatry Res , 2021 , 305 : 114252 .

WALSH A D , STONE S , FREYTAG S , et al . Mouse microglia express unique miRNA⁃mRNA networks to facilitate age⁃specific functions in the developing central nervous system [J ] . Commun Biol , 2023 , 6 ( 1 ): 555 .

DASKALAKIS N P , PROVOST A C , HUNTER R G , et al . Noncoding RNAs: Stress, glucocorticoids, and posttraumatic stress disorder [J ] . Biol Psychiatry , 2018 , 83 ( 10 ): 849 ⁃ 865 .

NIETO⁃QUERO A , INFANTES⁃LÓPEZ M I , ZAMBRANA⁃INFANTES E , et al . Unveiling the secrets of the stressed hippocampus: Exploring proteomic changes and neurobiology of posttraumatic stress disorder [J ] . Cells , 2023 , 12 ( 18 ): 2290 .

江珊 , 王福顺 . 杏仁核在创伤后应激障碍发病机制中的作用 [J ] . 国际精神病学杂志 , 2022 , 49 ( 4 ): 583 ⁃ 586 .

JIANG S , WANG F S . The role of amygdala in the pathogenesis of post⁃traumatic stress disorder [J ] . J Int Psychiatry , 2022 , 49 ( 4 ): 583 ⁃ 586 .

ZHENG Y C , GARRETT M E , SUN D L , et al . Trauma and posttraumatic stress disorder modulate polygenic predictors of hippocampal and amygdala volume [J ] . Transl Psychiatry , 2021 , 11 ( 1 ): 637 .

WROCKLAGE K M , AVERILL L A , COBB SCOTT J , et al . Cortical thickness reduction in combat exposed U.S. veterans with and without PTSD [J ] . Eur Neuropsychopharmacol , 2017 , 27 ( 5 ): 515 ⁃ 525 .

王昊若 , 葛茜 , 吕海侠 . 创伤后应激障碍的记忆损害相关结构研究进展 [J ] . 国际精神病学杂志 , 2020 , 47 ( 1 ): 18 ⁃ 20 .

WANG H R , GE Q , LYU H X . Research progress on memory impairment related structures of post⁃traumatic stress disorder [J ] . J Int Psychiatry , 2020 , 47 ( 1 ): 18 ⁃ 20 .

GIRGENTI M J , DUMAN R S . Transcriptome alterations in posttraumatic stress disorder [J ] . Biol Psychiatry , 2018 , 83 ( 10 ): 840 ⁃ 848 .

DU K X , LU W , SUN Y , et al . mRNA and miRNA profiles in the nucleus accumbens are related to fear memory and anxiety induced by physical or psychological stress [J ] . J Psychiatr Res , 2019 , 118 : 44 ⁃ 65 .

FIORENZA A , LOPEZ⁃ATALAYA J P , ROVIRA V , et al . Blocking miRNA biogenesis in adult forebrain neurons enhances seizure susceptibility, fear memory, and food intake by increasing neuronal responsiveness [J ] . Cereb Cortex , 2016 , 26 ( 4 ): 1619 ⁃ 1633 .

MUIÑOS⁃GIMENO M , ESPINOSA⁃PARRILLA Y , GUIDI M , et al . Human microRNAs miR⁃22, miR⁃138⁃2, miR⁃148a, and miR⁃488 are associated with panic disorder and regulate several anxiety candidate genes and related pathways [J ] . Biol Psychiatry , 2011 , 69 ( 6 ): 526 ⁃ 533 .

XU X F , WANG Y C , ZONG L , et al . MiR⁃151⁃5p modulates APH1a expression to participate in contextual fear memory formation [J ] . RNA Biol , 2019 , 16 ( 3 ): 282 ⁃ 294 .

XU X F , JING X , MA H X , et al . MiR⁃181a participates in contextual fear memory formation via activating mTOR signaling pathway [J ] . Cereb Cortex , 2018 , 28 ( 9 ): 3309 ⁃ 3321 .

LIN Q , WEI W , COELHO C M , et al . The brain⁃specific microRNA miR⁃128b regulates the formation of fear⁃extinction memory [J ] . Nat Neurosci , 2011 , 14 ( 9 ): 1115 ⁃ 1117 .

JONES M E , SILLIVAN S E , JAMIESON S , et al . MicroRNA mir⁃598⁃3p mediates susceptibility to stress enhancement of remote fear memory [J ] . Learn Mem , 2019 , 26 ( 9 ): 363 ⁃ 372 .

KONOPKA W , KIRYK A , NOVAK M , et al . MicroRNA loss enhances learning and memory in mice [J ] . J Neurosci , 2010 , 30 ( 44 ): 14835 ⁃ 14842 .

ZHAO C , ZHOU B , CAO J J , et al . MiR⁃187⁃3p participates in contextual fear memory formation through modulating SATB2 expression in the hippocampus [J ] . Neuroreport , 2020 , 31 ( 12 ): 909 ⁃ 917 .

D'ELIA A T D , JURUENA M F , COIMBRA B M , et al . Posttraumatic stress disorder (PTSD) and depression severity in sexually assaulted women: Hypothalamic⁃pituitary⁃adrenal (HPA) axis alterations [J ] . BMC Psychiatry , 2021 , 21 ( 1 ): 174 .

TANG Y X , CAI X J , ZHANG H W , et al . MiR⁃212 mediates counter⁃regulation on CRH expression and HPA axis activity in male mice [J ] . J Mol Endocrinol , 2017 , 59 ( 4 ): 365 ⁃ 375 .

PAN⁃VAZQUEZ A , RYE N , AMERI M , et al . Impact of voluntary exercise and housing conditions on hippocampal glucocorticoid receptor, miR⁃124 and anxiety [J ] . Mol Brain , 2015 , 8 : 40 .

XU J J , WANG R , LIU Y , et al . FKBP5 and specific microRNAs via glucocorticoid receptor in the basolateral amygdala involved in the susceptibility to depressive disorder in early adolescent stressed rats [J ] . J Psychiatr Res , 2017 , 95 : 102 ⁃ 113 .

YOSHINO Y , ROY B , DWIVEDI Y . Corticosterone⁃mediated regulation and functions of miR⁃218⁃5p in rat brain [J ] . Sci Rep , 2022 , 12 ( 1 ): 194 .

PASSOS I C , VASCONCELOS⁃MORENO M P , COSTA L G , et al . Inflammatory markers in post⁃traumatic stress disorder: A systematic review, meta⁃analysis, and meta⁃regression [J ] . Lancet Psychiatry , 2015 , 2 ( 11 ): 1002 ⁃ 1012 .

BUSBEE P B , BAM M , YANG X M , et al . Dysregulated TP53 among PTSD patients leads to downregulation of miRNA let⁃7a and promotes an inflammatory Th17 phenotype [J ] . Front Immunol , 2022 , 12 : 815840 .

BAM M , YANG X M , BUSBEE B P , et al . Increased H3K4me3 methylation and decreased miR⁃7113⁃5p expression lead to enhanced Wnt/β⁃catenin signaling in immune cells from PTSD patients leading to inflammatory phenotype [J ] . Mol Med , 2020 , 26 ( 1 ): 110 .

BAM M , YANG X , ZUMBRUN E E , et al . Decreased AGO2 and DCR1 in PBMCs from War Veterans with PTSD leads to diminished miRNA resulting in elevated inflammation [J ] . Transl Psychiatry , 2017 , 7 ( 8 ): e1222 .

SCHMIDT U , HERRMANN L , HAGL K , et al . Therapeutic action of fluoxetine is associated with a reduction in prefrontal cortical miR⁃1971 expression levels in a mouse model of posttraumatic stress disorder [J ] . Front Psychiatry , 2013 , 4 : 66 .

SONG J , KIM Y K . Identification of the role of miR⁃142⁃5p in Alzheimer's disease by comparative bioinformatics and cellular analysis [J ] . Front Mol Neurosci , 2017 , 10 : 227 .

JI L L , YE Y , NIE P Y , et al . Dysregulation of miR⁃142 results in anxiety⁃like behaviors following single prolonged stress [J ] . Behav Brain Res , 2019 , 365 : 157 ⁃ 163 .

陈欢 . FMRP通过miR⁃125a介导雄激素对海马突触可塑性和孤独症样行为的影响 [D ] . 石家庄 : 河北医科大学 , 2022 .

CHEN H . FMRP mediates the effects of androgen on synaptic plasticity and autism⁃like behavior in hippocampus through miR⁃125a [D ] . Shijiazhuang : Hebei Medical University , 2022 .

NIE P Y , TONG L , LI M D , et al . MiR⁃142 downregulation alleviates rat PTSD⁃like behaviors, reduces the level of inflammatory cytokine expression and apoptosis in hippocampus, and upregulates the expression of fragile X mental retardation protein [J ] . J Neuroinflammation , 2021 , 18 ( 1 ): 17 .

李明达 , 李纪萌 , 季丽莉 . Anti⁃miR⁃142上调前额叶皮质FMRP改善PTSD大鼠焦虑样行为 [J ] . 解剖科学进展 , 2022 , 28 ( 3 ): 307 ⁃ 310 .

LI M D , LI J M , JI L L . Anti⁃miR⁃142 ameliorates anxiety⁃like behavior through upregulating fragile X mental retardation protein in prefrontal cortex of PTSD rats [J ] . Prog Anat Sci , 2022 , 28 ( 3 ): 307 ⁃ 310 .

RONOVSKY M , ZAMBON A , CICVARIC A , et al . A role for miR⁃132 in learned safety [J ] . Sci Rep , 2019 , 9 ( 1 ): 528 .

彭军波 , 季丽莉 . Anti⁃miR⁃132通过结合FXR1减轻PTSD大鼠焦虑及抑郁样行为的实验研究 [J ] . 解剖科学进展 , 2023 , 29 ( 3 ): 325 ⁃ 328 .

PENG J B , JI L L . Anti⁃miR⁃132 alleviated anxiety and depression⁃like behaviors of PTSD rats by binding to FXR1 levels [J ] . Prog Anat Sci , 2023 , 29 ( 3 ): 325 ⁃ 328 .

NIE P Y , JI L L , FU C H , et al . MiR⁃132 regulates PTSD⁃like behaviors in rats following single⁃prolonged stress through fragile X⁃related protein 1 [J ] . Cell Mol Neurobiol , 2021 , 41 ( 2 ): 327 ⁃ 340 .

TONG L , LI M D , NIE P Y , et al . MiR⁃132 downregulation alleviates behavioral impairment of rats exposed to single prolonged stress, reduces the level of apoptosis in PFC, and upregulates the expression of MeCP2 and BDNF [J ] . Neurobiol Stress , 2021 , 14 : 100311 .

JI L L , PENG J B , FU C H , et al . Activation of sigma⁃1 receptor ameliorates anxiety⁃like behavior and cognitive impairments in a rat model of post⁃traumatic stress disorder [J ] . Behav Brain Res , 2016 , 311 : 408 ⁃ 415 .

CHEN Y L , TONG L , CHEN Y , et al . MiR⁃153 downregulation alleviates PTSD⁃like behaviors and reduces cell apoptosis by upregulating the sigma⁃1 receptor in the hippocampus of rats exposed to single⁃prolonged stress [J ] . Exp Neurol , 2022 , 352 : 114034 .

马璐璐 , 付文玉 , 庄文欣 , 等 . 帕金森病大鼠中缝背核内5⁃HT、CRF及其受体CRFR2的表达变化 [J ] . 神经解剖学杂志 , 2014 , 30 ( 4 ): 463 ⁃ 468 .

MA L L , FU W Y , ZHUANG W X , et al . Expression changes of 5⁃TH, CRF and CRFR2 in the dorsal raphe nucleus of rats with Parkinson's disease [J ] . Chin J Neuroanat , 2014 , 30 ( 4 ): 463 ⁃ 468 .

LIU Y , LIU D X , XU J J , et al . Early adolescent stress⁃induced changes in prefrontal cortex miRNA⁃135a and hippocampal miRNA⁃16 in male rats [J ] . Dev Psychobiol , 2017 , 59 ( 8 ): 958 ⁃ 969 .

LI C T , LIU Y , LIU D X , et al . Dynamic alterations of miR⁃34c expression in the hypothalamus of male rats after early adolescent traumatic stress [J ] . Neural Plast , 2016 , 2016 : 5249893 .

ZHU J , CHEN Z J , TIAN J X , et al . MiR⁃34b attenuates trauma⁃induced anxiety⁃like behavior by targeting CRHR1 [J ] . Int J Mol Med , 2017 , 40 ( 1 ): 90 ⁃ 100 .

张晗 , 刘士嘉 , 王胜强 , 等 . PTSD相关基因的研究进展 [J ] . 解剖科学进展 , 2016 , 22 ( 5 ): 543 ⁃ 545 .

ZHANG H , LIU S J , WANG S Q , et al . The progress of PTSD related genes [J ] . Prog Anat Sci , 2016 , 22 ( 5 ): 543 ⁃ 545 .

田萧羽 , 刘梦楠 , 方文灿 , 等 . FKBP5调控创伤后应激障碍的神经机制 [J ] . 中国药理学与毒理学杂志 , 2023 , 37 ( 7 ): 535 .

TIAN X Y , LIU M N , FANG W C , et al . Neural mechanism of FKBP5 regulating post⁃traumatic stress disorder [J ] . Chin J Pharmacol Toxicol , 2023 , 37 ( 7 ): 535 .

KANG H J , YOON S , LEE S J , et al . FKBP5⁃associated miRNA signature as a putative biomarker for PTSD in recently traumatized individuals [J ] . Sci Rep , 2020 , 10 ( 1 ): 3353 .

MAUREL O M , TORRISI S A , BARBAGALLO C , et al . Dysregulation of miR⁃15a⁃5p, miR⁃497a⁃5p and miR⁃511⁃5p is associated with modulation of BDNF and FKBP5 in brain areas of PTSD⁃related susceptible and resilient mice [J ] . Int J Mol Sci , 2021 , 22 ( 10 ): 5157 .

ZHENG D L , SABBAGH J J , BLAIR L J , et al . MicroRNA⁃511 binds to FKBP5 mRNA, which encodes a chaperone protein, and regulates neuronal differentiation [J ] . J Biol Chem , 2016 , 291 ( 34 ): 17897 ⁃ 17906 .

PARK J , LEE J , CHOI K , et al . Regulation of behavioral response to stress by microRNA⁃690 [J ] . Mol Brain , 2021 , 14 ( 1 ): 7 .

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