MiRNA‐199a‐5p targets WNT2 to regulate depression through the CREB/BDNF signaling in hippocampal neuron
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Introduction: This study mainly investigated the role of miR‐199a‐5p in depression. Methods: qRT‐PCR and western blotting were employed to detect the expressions of miR‐199a‐5p, CREB and BDNF. Sucrose preference test, forced swimming test, and tail suspension test were performed to evaluate depression‐related symptoms. MTT assays and flow cytometry were used to examine the cell reproduction and apoptotic cells of hippocampal neuron. Results: The data demonstrated that the expression levels of miR‐199a‐5p in the cerebrospinal fluids and serums of depression patient and the hippocampus of chronic unpredictable mild stress (CUMS) mouse were significantly increased. However, the expressions of WNT2, p‐CREB, and BDNF were inhibited. In addition, miR‐199a‐5p‐inhibitor enhanced sucrose preferences of CUMS mouse and decreased immobile time in sucrose preference test and forced swimming test. Knockdown of WNT2 attenuated the effects of miR‐199a‐5p‐inhibitor on cell reproduction and apoptotic cells of hippocampal neuron and the expression of WNT2, p‐CREB, and BDNF. Conclusion: MiR‐199a‐5p can target WNT2 to enhance the development of depression through regulation of the CREB/BDNF signaling. Trial registration: JNU‐Hos‐49284.
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In depression, more miR-199a-5p was noted in microglia, suppressing WNT2 expression through CREB/BDNF signaling regulation.
“In depression, more miR-199a-5p was noted in microglia suppressing WNT2 expression through the CREB/BDNF signaling regulation.270”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [270]
The Abstract Results report increased miR-199a-5p in patients’ cerebrospinal fluid and serum and in the hippocampus of depressed mice. The Conclusions state that miR-199a-5p targets WNT2 through CREB/BDNF signaling, but the paper studies hippocampal neurons, not increased miR-199a-5p in microglia. Page numbers are unavailable in our copy. (LLM, conf=0.90)
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Blood microRNA changes in depressed patients during antidepressant treatment
Bocchio-Chiavetto, L., Maffioletti, E., Bettinsoli, P., Giovannini, C., Bignotti, S., Tardito, D., Corrada, D., Milanesi, L., & Gennarelli, M. (2013) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2012.06.013 · Cited by 238 · see citing works
An updated role of microRNA-124 in central nervous system disorders: a review
Sun, Y., Luo, Z.-M., Guo, X.-M., Su, D.-F., & Liu, X. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00193 · Cited by 223 · see citing works
Identification of MicroRNA-124-3p as a Putative Epigenetic Signature of Major Depressive Disorder
Roy, B., Dunbar, M., Shelton, R. C., & Dwivedi, Y. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.175 · Cited by 199 · see citing works
Emerging role of microRNAs in major depressive disorder: diagnosis and therapeutic implications
Dwivedi, Y. (2014) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2014.16.1/ydwivedi · Cited by 169 · see citing works
Hippocampal MicroRNA-124 Enhances Chronic Stress Resilience in Mice
Higuchi, F., Uchida, S., Yamagata, H., Abe-Higuchi, N., Hobara, T., Hara, K., Kobayashi, A., Shintaku, T., Itoh, Y., Suzuki, T., et al. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.0319-16.2016 · Cited by 158 · see citing works
Xu, Y., Liu, H., Li, F., Sun, N., Ren, Y., Liu, Z., Cao, X., Wang, Y., Liu, P., & Zhang, K. (2010) · Journal of Affective Disorders · doi:10.1016/j.jad.2010.05.019 · Cited by 99 · see citing works
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Research works printed but not linked: 22
- Castren, E. (2013). Neuronal network plasticity and recovery from depression. JAMA Psychiatry, 70(9), 983– 989. 10.1001/jamapsychiatry.2013.1 23842648 · DOI · Paper page
- Cheng, A. M., Byrom, M. W., Shelton, J., & Ford, L. P. (2005). Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Research, 33(4), 1290– 1297. 10.1093/nar/gki200 15741182 PMC552951 · DOI
- Dowlatshahi, D., MacQueen, G. M., Wang, J. F., & Young, L. T. (1998). Increased temporal cortex CREB concentrations and antidepressant treatment in major depression. Lancet, 352(9142), 1754. 9848357
- Fang, Y., Qiu, Q., Zhang, S., Sun, L., Li, G., Xiao, S., & Li, X. (2018). Changes in miRNA‐132 and miR‐124 levels in non‐treated and citalopram‐treated patients with depression. Journal of Affective Disorders, 227, 745– 751. 10.1016/j.jad.2017.11.090 29689690 · DOI · Paper page
- Gheinani, A. H., Burkhard, F. C., Rehrauer, H., Fournier, C. A., & Monastyrskaya, K. (2015). MicroRNA MiR‐199a‐5p regulates smooth muscle cell proliferation and morphology by targeting WNT2 signaling pathway. Journal of Biological Chemistry, 290(11), 7067– 7086. 10.1074/jbc.M114.618694 PMC4358129 25596533 · DOI
- Huelsken, J., & Behrens, J. (2002). The Wnt signalling pathway. Journal of Cell Science, 115(21), 3977– 3978. 10.1242/jcs.00089 12356903 · DOI
- Juhasz, G., Dunham, J. S., McKie, S., Thomas, E., Downey, D., Chase, D., Lloyd‐Williams, K., Toth, Z. G., Platt, H., Mekli, K., Payton, A., Elliott, R., Williams, S. R., Anderson, I. M., & Deakin, J. F. W. (2011). The CREB1‐BDNF‐NTRK2 pathway in depression: Multiple gene‐cognition‐environment interactions. Biological Psychiatry, 69(8), 762– 771. 10.1016/j.biopsych.2010.11.019 21215389 · DOI
- Kosik, K. S. (2006). The neuronal microRNA system. Nature Reviews Neuroscience, 7(12), 911. 10.1038/nrn2037 17115073 · DOI
- La Torre, A., Georgi, S., & Reh, T. A. (2013). Conserved microRNA pathway regulates developmental timing of retinal neurogenesis. Proceedings of the National Academy of Sciences, 110(26), E2362– E2370. 10.1073/pnas.1301837110 PMC3696811 23754433 · DOI
- Lopez, J. P., Lim, R., Cruceanu, C., Crapper, L., Fasano, C., Labonte, B., Maussion, G., Yang, J. P., Yerko, V., Vigneault, E., El Mestikawy, S., Mechawar, N., Pavlidis, P., & Turecki, G. (2014). miR‐1202 is a primate‐specific and brain‐enriched microRNA involved in major depression and antidepressant treatment. Nature Medicine, 20(7), 764. 10.1038/nm.3582 PMC4087015 24908571 · DOI · Paper page
- Martins, M., Rosa, A., Guedes, L. C., Fonseca, B. V., Gotovac, K., Violante, S., Mestre, T., Coelho, M., Rosa, M. M., Martin, E. R., Vance, J. M., Outeiro, T. F., Wang, L., Borovecki, F., Ferreira, J. J., & Oliveira, S. A. (2011). Convergence of miRNA expression profiling, α‐synuclein interacton and GWAS in Parkinson's disease. PLoS One, 6(10), e25443.– 10.1371/journal.pone.0025443 22003392 PMC3189215 · DOI
- Moussavi, S., Chatterji, S., Verdes, E., Tandon, A., Patel, V., & Ustun, B. (2007). Depression, chronic diseases, and decrements in health: Results from the World Health Surveys. The Lancet, 370(9590), 851– 858. 17826170
- Qi, X., Lin, W., Li, J., Li, H., Wang, W., Wang, D., & Sun, M. (2008). Fluoxetine increases the activity of the ERK‐CREB signal system and alleviates the depressive‐like behavior in rats exposed to chronic forced swim stress. Neurobiology of Disease, 31(2), 278– 285. 10.1016/j.nbd.2008.05.003 18586506 · DOI
- Raimondi, L., Amodio, N., Di Martino, M. T., Altomare, E., Leotta, M., Caracciolo, D., & D'Aquila, P. (2014). Targeting of multiple myeloma‐related angiogenesis by miR‐199a‐5p mimics: In vitro and in vivo anti‐tumor activity. Oncotarget, 5(10), 3039. 24839982 PMC4102790
- Roy, B., Wang, Q., Palkovits, M., Faludi, G., & Dwivedi, Y. (2017). Altered miRNA expression network in locus coeruleus of depressed suicide subjects. Scientific Reports, 7(1), 4387., 10.1038/s41598-017-04300-9 28663595 PMC5491496 · DOI · Paper page
- Strine, T. W., Kroenke, K., Dhingra, S., Balluz, L. S., Gonzalez, O., Berry, J. T., & Mokdad, A. H. (2009). The associations between depression, health‐related quality of life, social support, life satisfaction, and disability in community‐dwelling US adults. The Journal of Nervous and Mental Disease, 197(1), 61– 64. 10.1097/NMD.0b013e3181924ad8 19155812 · DOI
- Sun, L., Zhu, J., Wu, M., Sun, H., Zhou, C., Fu, L., & Mei, C. (2015). Inhibition of MiR‐199a‐5p reduced cell proliferation in autosomal dominant polycystic kidney disease through targeting CDKN1C. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 21, 195. 25588980 PMC4304454
- Voleti, B., & Duman, R. (2012). The roles of neurotrophic factor and Wnt signaling in depression. Clinical Pharmacology & Therapeutics, 91(2), 333– 338. 10.1038/clpt.2011.296 22205198 · DOI
- Wan, Y., Liu, Y., Wang, X., Wu, J., Liu, K., Zhou, J., Liu, L. I., & Zhang, C. (2015). Identification of differential microRNAs in cerebrospinal fluid and serum of patients with major depressive disorder. PLoS One, 10(3), e0121975.– 10.1371/journal.pone.0121975 25763923 PMC4357380 · DOI · Paper page
- Xu, P., Vernooy, S. Y., Guo, M., & Hay, B. A. (2003). The Drosophila microRNA Mir‐14 suppresses cell death and is required for normal fat metabolism. Current Biology, 13(9), 790– 795. 10.1016/S0960-9822(03)00250-1 12725740 · DOI
- Yi, H., Liang, B., Jia, J., Liang, N., Xu, H., Ju, G., Ma, S., & Liu, X. (2013). Differential roles of miR‐199a‐5p in radiation‐induced autophagy in breast cancer cells. FEBS Letters, 587(5), 436– 443. 10.1016/j.febslet.2012.12.027 23337876 · DOI
- Yi, L.‐T., Li, J., Liu, B.‐B., Luo, L., Liu, Q., & Geng, D. (2014). BDNF–ERK–CREB signalling mediates the role of miR‐132 in the regulation of the effects of oleanolic acid in male mice. Journal of Psychiatry & Neuroscience: JPN, 39(5), 348. 10.1503/jpn.130169 25079084 PMC4160364 · DOI
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Yuan, M., Yang, B., Rothschild, G., Mann, J. J., Sanford, L. D., Tang, X., Huang, C., Wang, C., & Zhang, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01519-z · Cited by 246 · see citing works
“270 The downregulation of miR-124 in depression also promotes the activation of BV2 microglia by activating STAT3.”
Background
- Authors
- Liu, Z., Yang, J., Fang, Q., Shao, H., Yang, D., Sun, J., & Gao, L.
- Affiliations
- Baotou Medical College (CN)
- Tianjin Medical University General Hospital (CN)
- Department of department of neurology The Second Affiliated Hospital of Baotou Medical College Baotou China
- Corresponding author
- Yang, Jianli
- Venue
- Brain and Behavior
- Publisher
- Wiley
- Published
- 2021-08
- Volume
- 11
- Issue
- 8
- Pages
- e02107-e02107
- ISSN
- 2157-9032 (ISSN-L)
- 2162-3279
- PMC
- PMC8413827
- OpenAlex
- W3192802547
- Cited by
- 22
- References
- 6
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 7 · 2023: 6 · 2022: 3
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Brain and Behavior (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- miR-199a-5p, Wnt2, depression, CREB/BDNF signaling, hippocampal neurons, chronic unpredictable mild stress, neuronal apoptosis, microRNA target regulation, depression biomarkers
- MeSH terms
- Animals, Depression, Hippocampus, Humans, Neurons, Brain-Derived Neurotrophic Factor, MicroRNAs, Wnt2 Protein, Mice
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