CoChat
Sign Up
Cited by 20Treatment of Major DepressionCancer-related molecular mechanisms researchStress Responses and Cortisol

Fluoxetine ameliorates depressive symptoms by regulating lncRNA expression in the mouse hippocampus

Open access
Zhang, Chuan-Ling, 中国科学院昆明植物研究所植物化学与西部植物资源持续利用国家重点实验室，云南省天然药物化学重点实验室，云南 昆明650201，中国, State Key Laboratory of Phytochemistry and Plant Resources in West China, Yunnan Key Laboratory of Natural Medical Chemistry, Kunming Institute of Botany, the Chinese Academy of Sciences, Kunming, Yunnan 650201, China, Li, Yi-Jia, Lu, Shuang, Zhang, Ting, Xiao, Rui, Luo, Huai-Rong +8 more·2021·Zoological Research
DOI 10.24272/j.issn.2095-8137.2020.294PMC PMC7840451
Open this paper in CoChat — free account

Abstract

Depression is a prevalent mental disorder that is associated with aging and contributes to increased mortality and morbidity. The overall prevalence of geriatric depression with clinically significant symptoms is currently on the rise. Recent studies have demonstrated that altered expressions of long non-coding RNAs (lncRNAs) in the brain affect neurodevelopment and manifest modulating functions during the depression. However, most lncRNAs have not yet been studied. Herein, we analyzed the transcriptome of dysregulated lncRNAs to reveal their expressions in a mouse model exhibiting depressive-like behaviors, as well as their corresponding response following antidepressant fluoxetine treatment. A chronic unpredictable mild stress (CUMS) mouse model was applied. A six-week fluoxetine intervention in CUMS-induced mice attenuated depressive-like behaviors. In addition, differential expression analysis of lncRNAs was performed following RNA-sequencing. A total of 282 lncRNAs (134 up-regulated and 148 down-regulated) were differentially expressed in CUMS-induced mice relative to non-stressed counterparts (P<0.05). Moreover, 370 differentially expressed lncRNAs were identified in CUMS-induced mice after fluoxetine intervention. Gene Ontology (GO) analyses showed an association between significantly dysregulated lncRNAs and protein binding, oxygen binding, and transport activity, while the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that these dysregulated lncRNAs might be involved in inflammatory response pathways. Fluoxetine effectively ameliorated the symptoms of depression in CUMS-induced mice by regulating the expression of lncRNAs in the hippocampus. The findings herein provide valuable insights into the potential mechanism underlying depression in elderly people.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.24272/j.issn.2095-8137.2020.294

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 55 · Cited by 20

Research works printed but not linked: 52

  1. [1]Angelucci F, Aloe L, Jiménez-Vasquez P, Mathé AA Electroconvulsive stimuli alter the regional concentrations of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor in adult rat brain The Journal of ECT 2002 18 3 138 143 10.1097/00124509-200209000-00005 12394532 · DOI
  2. [2]Beyer JL Managing depression in geriatric populations Annals of Clinical Psychiatry 2007 19 4 221 238 10.1080/10401230701653245 18058280 · DOI
  3. [3]Blazer DG Depression in late life: review and commentary The Journals of Gerontology: Series A 2003 58 3 M249 M265 10.1093/gerona/58.3.M249 12634292 · DOI
  4. [4]Bramham CR, Messaoudi E BDNF function in adult synaptic plasticity: the synaptic consolidation hypothesis Progress in Neurobiology 2005 76 2 99 125 10.1016/j.pneurobio.2005.06.003 16099088 · DOI · Paper page
  5. [5]Bremner JD Fluoxetine in depressed patients: a comparison with imipramine The Journal of Clinical Psychiatry 1984 45 10 414 419 6384203
  6. [6]Brunoni AR, Lopes M, Fregni F A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression International Journal of Neuropsychopharmacology 2008 11 8 1169 1180 10.1017/S1461145708009309 18752720 · DOI · Paper page
  7. [7]Camkurt MA, Acar Ş, Coşkun S, Güneş M, Güneş S, Yılmaz MF, et al Comparison of plasma MicroRNA levels in drug naive, first episode depressed patients and healthy controls Journal of Psychiatric Research 2015 69 67 71 26343596
  8. [8]Casey DA Depression in the elderly South Medcal Jounal 1994 87 5 559 563 8178211
  9. [9]Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, Chinappi M, et al A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA Cell 2011 147 2 358 369 22000014 PMC3234495
  10. [10]Chen DM, Meng L, Pei F, Zheng Y, Leng JY A review of DNA methylation in depression Journal of Clinical Neuroscience 2017 43 39 46 28645747
  11. [11]Chen Z, Bu NP, Qiao XH, Zuo ZX, Shu YH, Liu ZL, et al Forkhead Box M1 transcriptionally regulates the expression of long noncoding RNAs Snhg8 and Gm26917 to promote proliferation and survival of muscle satellite cells Stem Cells 2018 36 7 1097 1108 29575305
  12. [12]Cryan JF, Mombereau C, Vassout A The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice Neuroscience & Biobehavioral Reviews 2005 29 4–5 571 625 15890404
  13. [13]Cui XL, Sun XY, Niu W, Kong LM, He MJ, Zhong AF., et al Long non-coding RNA: potential diagnostic and therapeutic biomarker for major depressive disorder Medical Science Monitor 2016 22 5240 5248 28039689 PMC5221417
  14. [15]Flurkey K, Currer JM, Harrison DE. 2007. Mouse models in aging research. In: Fox JG, Davisson MT, Quimby FW, Barthold SW, Newcomer CE, Smith AL. The Mouse in Biomedical Research. 2nd ed. Amsterdam: Elsevier, 637−672.
  15. [16]Gibbons A, Udawela M, Dean B Non-coding RNA as novel players in the pathophysiology of schizophrenia Non-Coding RNA 2018 4 2 11 PMC6027250 29657307
  16. [17]Guil S, Esteller M Cis-acting noncoding RNAs: friends and foes Nature Structural & Molecular Biology 2012 19 11 1068 1075 23132386
  17. [18]Gururajan A, Clarke G, Dinan TG, Cryan JF Molecular biomarkers of depression Neuroscience & Biobehavioral Reviews 2016 64 101 133 26906761
  18. [19]Hiles SA, Baker AL, de Malmanche T, Attia J Interleukin-6, C-reactive protein and interleukin-10 after antidepressant treatment in people with depression: a meta-analysis Psychological Medicine 2012 42 10 2015 2026 10.1017/S0033291712000128 22336436 · DOI
  19. [20]Huang X, Luo YL, Mao YS, Ji JL The link between long noncoding RNAs and depression Progress in Neuro-Psychopharmacology and Biological Psychiatry 2017 73 73 78 10.1016/j.pnpbp.2016.06.004 27318257 · DOI
  20. [21]Huang XY, Sun WY, Yan ZQ, Shi HR, Yang QL, Wang PF, et al Integrative analyses of long non-coding RNA and mRNA involved in piglet ileum immune response to Clostridium perfringens Type C infection Frontiers in Cellular and Infection Microbiology 2019 9 130 31114763 PMC6503642
  21. [22]Jani BD, McLean G, Nicholl BI, Barry SJE, Sattar N, Mair FS, et al Risk assessment and predicting outcomes in patients with depressive symptoms: a review of potential role of peripheral blood based biomarkers Frontiers in Human Neuroscience 2015 9 18 25698954 PMC4313702
  22. [23]Kim D, Paggi JM, Park C, Bennett C, Salzberg SL Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype Nature Biotechnology 2019 37 8 907 915 10.1038/s41587-019-0201-4 PMC7605509 31375807 · DOI · Paper page
  23. [24]Kong L, Zhang Y, Ye ZQ, Liu XQ, Zhao SQ, Wei LP, et al CPC: assess the protein-coding potential of transcripts using sequence features and support vector machine Nucleic Acids Research 2007 35 S2 W345 W349 17631615 PMC1933232
  24. [25]Leung AKL, Sharp PA MicroRNA functions in stress responses Molecular Cell 2010 40 2 205 215 10.1016/j.molcel.2010.09.027 20965416 PMC2996264 · DOI · Paper page
  25. [26]Lin MF, Jungreis I, Kellis M PhyloCSF: a comparative genomics method to distinguish protein coding and non-coding regions Bioinformatics 2011 27 13 i275 i282 21685081 PMC3117341
  26. [27]Liu MY, Yin CY, Zhu LJ, Zhu XH, Xu C, Luo CX, et al Sucrose preference test for measurement of stress-induced anhedonia in mice Nature Protocols 2018 13 7 1686 1698 10.1038/s41596-018-0011-z 29988104 · DOI · Paper page
  27. [28]Liu ZF, Li XR, Sun N, Xu Y, Meng YQ, Yang CX, et al Microarray profiling and co-expression network analysis of circulating lncRNAs and mRNAs associated with major depressive disorder PLoS One 2014 9 3 e93388 10.1371/journal.pone.0093388 24676134 PMC3968145 · DOI
  28. [29]Lopez JP, Fiori LM, Cruceanu C, Lin RX, Labonte B, Cates HM, et al MicroRNAs 146a/b-5 and 425–3p and 24–3p are markers of antidepressant response and regulate MAPK/Wnt-system genes Nature Communications 2017 8 15497 10.1038/ncomms15497 PMC5477510 28530238 · DOI · Paper page
  29. [30]López-Muñoz F, Alamo C Monoaminergic neurotransmission: the history of the discovery of antidepressants from 1950s until today Current Pharmaceutical Design 2009 15 14 1563 1586 19442174
  30. [31]Maes M, Smith R, Scharpe S The monocyte-T-lymphocyte hypothesis of major depression Psychoneuroendocrinology 1995 20 2 111 116 10.1016/0306-4530(94)00066-J 7899532 · DOI · Paper page
  31. [33]Neto FL, Borges G, Torres-Sanchez S, Mico JA, Berrocoso E Neurotrophins role in depression neurobiology: a review of basic and clinical evidence Current Neuropharmacology 2011 9 4 530 552 10.2174/157015911798376262 22654714 PMC3263450 · DOI
  32. [34]Ni XQ, Liao YZ, Li LM, Zhang XL, Wu ZZ Therapeutic role of long non-coding RNA TCONS_00019174 in depressive disorders is dependent on Wnt/β-catenin signaling pathway Journal of Integrative Neuroscience 2018 17 2 125 132 29036835
  33. [35]Nollet M, Le Guisquet AM, Belzung C Models of depression: unpredictable chronic mild stress in mice Current Protocols in Pharmacology 2013 61 1 5.65 23744712
  34. [36]Perez-Caballero L, Torres-Sanchez S, Bravo L, Mico JA, Berrocoso E Fluoxetine: a case history of its discovery and preclinical development Expert Opinion on Drug Discovery 2014 9 5 567 578 10.1517/17460441.2014.907790 24738878 · DOI
  35. [37]Pertea M, Pertea GM, Antonescu CM, Chang TC, Mendell JT, Salzberg SL StringTie enables improved reconstruction of a transcriptome from RNA-seq reads Nature Biotechnology 2015 33 3 290 295 10.1038/nbt.3122 PMC4643835 25690850 · DOI
  36. [38]Punta M, Coggill PC, Eberhardt RY, Mistry J, Tate J, Boursnell C, et al The Pfam protein families database Nucleic Acids Research 2012 40 Database issue D290 D301 22127870 PMC3245129
  37. [39]Raedler TJ Inflammatory mechanisms in major depressive disorder Current Opinion in Psychiatry 2011 24 6 519 525 10.1097/YCO.0b013e32834b9db6 21897249 · DOI
  38. [40]Raison CL, Capuron L, Miller AH Cytokines sing the blues: inflammation and the pathogenesis of depression Trends in Immunology 2006 27 1 24 31 10.1016/j.it.2005.11.006 16316783 PMC3392963 · DOI · Paper page
  39. [41]Riva P, Ratti A, Venturin M The long non-coding RNAs in neurodegenerative diseases: novel mechanisms of pathogenesis Current Alzheimer Research 2016 13 11 1219 1231 27338628
  40. [42]Robinson MD, McCarthy DJ, Smyth GK edgeR: a Bioconductor package for differential expression analysis of digital gene expression data Bioinformatics 2010 26 1 139 140 10.1093/bioinformatics/btp616 19910308 PMC2796818 · DOI · Paper page
  41. [43]Roy B, Wang QZ, Dwivedi Y Long noncoding RNA-Associated transcriptomic changes in resiliency or susceptibility to depression and response to antidepressant treatment The International Journal of Neuropsychopharmacology 2018 21 5 461 472 10.1093/ijnp/pyy010 29390069 PMC5932471 · DOI
  42. [44]Sampson SM Treating depression with selective serotonin reuptake inhibitors: a practical approach Mayo Clinic Proceedings 2001 76 7 739 744 11444407
  43. [45]Sen S, Duman R, Sanacora G Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications Biological Psychiatry 2008 64 6 527 532 10.1016/j.biopsych.2008.05.005 18571629 PMC2597158 · DOI · Paper page
  44. [48]Strawbridge R, Young AH, Cleare AJ Biomarkers for depression: recent insights, current challenges and future prospects Neuropsychiatric Disease and Treatment 2017 13 1245 1262 10.2147/NDT.S114542 28546750 PMC5436791 · DOI · Paper page
  45. [49]Sun L, Luo HT, Bu DC, Zhao GG, Yu KT, Zhang CH, et al Utilizing sequence intrinsic composition to classify protein-coding and long non-coding transcripts Nucleic Acids Research 2013 41 17 e166 10.1093/nar/gkt646 23892401 PMC3783192 · DOI
  46. [51]Tang J, Yu YZ, Yang W Long noncoding RNA and its contribution to autism spectrum disorders CNS Neuroscience & Therapeutics 2017 23 8 645 656 28635106 PMC6492731
  47. [52]Wan YQ, Feng JG, Li M, Wang MZ, Liu L, Liu XR, et al Prefrontal cortex miR-29b-3p plays a key role in the antidepressant-like effect of ketamine in rats Experimental & Molecular Medicine 2018 50 10 1 14 PMC6204429 30369596
  48. [53]Wapinski O, Chang HY Long noncoding RNAs and human disease Trends in Cell Biology 2011 21 6 354 361 10.1016/j.tcb.2011.04.001 21550244 · DOI
  49. [54]Willner P, Towell A, Sampson D, Sophokleous S, Muscat R Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant Psychopharmacology 1987 93 3 358 364 3124165
  50. [55]Xiao R, Park Y, Dirisala VR, Zhang YP, Um SJ, Lee HT, et al Identification of genes differentially expressed in wild type and Purkinje cell degeneration mice Molecules and Cells 2005 20 2 219 227 16267396
  51. [56]Yalcin I, Belzung C, Surget A Mouse strain differences in the unpredictable chronic mild stress: a four-antidepressant survey Behavioural Brain Research 2008 193 1 140 143 10.1016/j.bbr.2008.04.021 18565601 · DOI
  52. [57]Yankelevitch-Yahav R, Franko M, Huly A, Doron R The forced swim test as a model of depressive-like behavior Journal of Visualized Experiments 2015 97 e52587 PMC4401172 25867960

Authors
Zhang, C.-L., 昆明650201，中国, 中., State Key Laboratory of Phytochemistry and Plant Resources in West China, Y. K. L. O. N. M. C., Li, Y.-J., Lu, S., Zhang, T., Xiao, R., Luo, H.-R., 呼和浩特010110，中国, 内., 中国科学院大学，北京100049，中国, 呼和浩特010059，中国, 内., 646000，中国, 西. 泸., School of Pharmacy, I. M. M. U., University of the Chinese Academy of Sciences, B. 1., Key Laboratory of Molecular Pathology, I. M. M. U., & Key Laboratory for Aging and Regenerative Medicine, D. O. P.
Affiliations
  • Inner Mongolia Medical University (CN)
  • Kunming Institute of Botany (CN)
Corresponding author
  • Xiao, Rui
  • Luo, Huai-Rong
ORCID
Venue
Zoological Research
Publisher
Zoological Research
Published
2021
Volume
42
Issue
1
Pages
28-42
ISSN
2095-8137 (ISSN-L)
DOI
10.24272/j.issn.2095-8137.2020.294
PMC
PMC7840451
OpenAlex
W3120019431
Cited by
20
References
55
Citations by year
2026: 5 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 6
FWCI
1.90
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • 动物学研究 (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
depression, fluoxetine, long non-coding RNA, hippocampus, chronic unpredictable mild stress, geriatric depression, antidepressant mechanism, lncRNA expression profiling, inflammation, differential gene expression
MeSH terms
Animals, Depressive Disorder, Fluoxetine, Hippocampus, Male, Mice, Inbred BALB C, Stress, Psychological, Antidepressive Agents, Second-Generation, Mice, RNA, Long Noncoding

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review