MicroRNA-mediated regulation of BDNF in depressive disorder: a pathway to diagnosis and therapy
DOI:
https://doi.org/10.31117/neuroscirn.v8i3.409Keywords:
Depression, MicroRNA, MiRNA, BDNF, Diagnosis, TreatmentAbstract
Depressive disorder, also known as depression, represents a major global health concern. Effective diagnosis and treatment of depression are critical to moderate its impact. Current diagnostic methods for depression are time-consuming and subjective, which can lead to misdiagnosis and impact treatment effectiveness. Therefore, identifying potential biomarkers for early and accurate diagnosis is critically needed. Although the exact pathophysiology of depression remains unknown, neurotrophic factors, with brain-derived neurotrophic factor (BDNF) being the most important, have been elucidated to play a key role in the pathogenesis of depression. Alterations in functional BDNF may contribute to the pathophysiology of depression by impairing neuroplasticity, a process closely linked to antidepressant action. Meanwhile, advancements in next-generation sequencing (NGS), quantitative polymerase chain reaction (qPCR), and bioinformatics have enabled the identification of various microRNAs (miRNAs) associated with depression. This review aims to assess the role and mechanisms of microRNAs that target BDNF in depression. These microRNAs regulate the pathophysiology of depression, particularly through abnormalities in neuroplasticity and neurogenesis, as well as other mechanisms such as hypothalamic-pituitary-adrenal axis hyperactivity and inflammatory dysregulation. These microRNAs may serve as biomarkers for diagnosis and as targets for novel antidepressants. Our study identifies 16 miRNAs that target BDNF in depression, either directly or indirectly through other molecules. Among these, miR-124, miR-132, and miR-221 are promising candidates for biomarkers of depression. Meanwhile, miR-124 and miR-132 present significant promise for treatment. However, major challenges remain in translating these findings into clinical practice, underscoring the need for further research.
References
Ahmadimanesh, M., Etemad, L., Rad, D. M., Ghahremani, M. H., Mohammadpour, A. H., Esfehani, R. J., Jowsey, P., Behdani, F., Moallem, S. A., & Abbaszadegan, M. R. (2023). Effect of citalopram and sertraline on the expression of miRNA- 124, 132, and 16 and their protein targets in patients with depression. Iranian Journal of Basic Medical Sciences, 26(7), 820–829. https://doi.org/10.22038/ijbms.2023.66496.14595
Bloodgood, B. L., Sharma, N., Browne, H. A., Trepman, A. Z., & Greenberg, M. E. (2013). The activity-dependent transcription factor NPAS4 regulates domain-specific inhibition. Nature, 503(7474), 121–125. https://doi.org/10.1038/nature12743
Casarotto, P. C., Girych, M., Fred, S. M., Kovaleva, V., Moliner, R., Enkavi, G., Biojone, C., Cannarozzo, C., Sahu, M. P., Kaurinkoski, K., Brunello, C. A., Steinzeig, A., Winkel, F., Patil, S., Vestring, S., Serchov, T., Diniz, C. R., Laukkanen, L., Cardon, I., . . . Castrén, E. (2021). Antidepressant drugs act by directly binding to TRKB neurotrophin receptors. Cell, 184(5), 1299-1313.e19. https://doi.org/10.1016/j.cell.2021.01.034
Casarotto, P., Umemori, J., & Castrén, E. (2022). BDNF receptor TrkB as the mediator of the antidepressant drug action. Frontiers in Molecular Neuroscience, 15, 1032224. https://doi.org/10.3389/fnmol.2022.1032224
Chang, C., Kuek, E. J. W., Su, C., & Gean, P. (2020). MicroRNA-206 regulates Stress-Provoked aggressive behaviors in post-weaning social isolation mice. Molecular Therapy — Nucleic Acids, 20, 812–822. https://doi.org/10.1016/j.omtn.2020.05.001
Cui, Y., Ma, G., Kong, F., & Song, L. (2021). Diagnostic values of miR-221-3p in serum and cerebrospinal fluid for post-stroke depression and analysis of risk factors. Iranian Journal of Public Health, 50(6), 1241-1249. https://doi.org/10.18502/ijph.v50i6.6423
Diener, C., Keller, A., & Meese, E. (2022). Emerging concepts of miRNA therapeutics: from cells to clinic. Trends in Genetics, 38(6), 613–626. https://doi.org/10.1016/j.tig.2022.02.006
Ding, R., Su, D., Zhao, Q., Wang, Y., Wang, J., Lv, S., & Ji, X. (2023). The role of microRNAs in depression. Frontiers in Pharmacology, 14, 1129186. https://doi.org/10.3389/fphar.2023.1129186
Duman, R. S., Deyama, S., & Fogaça, M. V. (2019). Role of BDNF in the pathophysiology and treatment of depression: Activity‐dependent effects distinguish rapid‐acting antidepressants. European Journal of Neuroscience, 53(1), 126–139. https://doi.org/10.1111/ejn.14630
Enatescu, V. R., Papava, I., Enatescu, I., Antonescu, M., Anghel, A., Seclaman, E., Sirbu, I. O., & Marian, C. (2016). Circulating plasma micro RNAs in patients with major depressive disorder treated with antidepressants: a pilot study. Psychiatry Investigation, 13(5), 549-557. https://doi.org/10.4306/pi.2016.13.5.549
Esvald, E., Tuvikene, J., Sirp, A., Patil, S., Bramham, C. R., & Timmusk, T. (2020). CREB family transcription factors are major mediators of BDNF transcriptional autoregulation in cortical neurons. Journal of Neuroscience, 40(7), 1405–1426. https://doi.org/10.1523/jneurosci.0367-19.2019
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. https://doi.org/10.1016/j.jad.2017.11.090
Friedman, R. C., Farh, K. K., Burge, C. B., & Bartel, D. P. (2009). Most mammalian mRNAs are conserved targets of microRNAs. Genome Research, 19(1), 92–105. https://doi.org/10.1101/gr.082701.108
Gao, Z., Chen, T., Yu, T., Zhang, L., Zhao, S., Gu, X., Pan, Y., & Kong, L. (2022). Cinnamaldehyde prevents intergenerational effect of paternal depression in mice via regulating GR/miR-190b/BDNF pathway. Acta Pharmacologica Sinica, 43(8), 1955–1969. https://doi.org/10.1038/s41401-021-00831-0
Gorinski, N., Bijata, M., Prasad, S., Wirth, A., Galil, D. A., Zeug, A., Bazovkina, D., Kondaurova, E., Kulikova, E., Ilchibaeva, T., Zareba-Koziol, M., Papaleo, F., Scheggia, D., Kochlamazashvili, G., Dityatev, A., Smyth, I., Krzystyniak, A., Wlodarczyk, J., Richter, D. W., . . . Ponimaskin, E. (2019). Attenuated palmitoylation of serotonin receptor 5-HT1A affects receptor function and contributes to depression-like behaviors. Nature Communications, 10(1), 3924. https://doi.org/10.1038/s41467-019-11876-5
Guan, W., Xu, D., Ji, C., Wang, C., Liu, Y., Tang, W., Gu, J., Chen, Y., Huang, J., Liu, J., & Jiang, B. (2021). Hippocampal miR-206-3p participates in the pathogenesis of depression via regulating the expression of BDNF. Pharmacological Research, 174, 105932. https://doi.org/10.1016/j.phrs.2021.105932
He, S., Liu, X., Jiang, K., Peng, D., Hong, W., Fang, Y., Qian, Y., Yu, S., & Li, H. (2016). Alterations of microRNA-124 expression in peripheral blood mononuclear cells in pre- and post-treatment patients with major depressive disorder. Journal of Psychiatric Research, 78, 65–71. https://doi.org/10.1016/j.jpsychires.2016.03.015
Hing, B., Sathyaputri, L., & Potash, J. B. (2018). A comprehensive review of genetic and epigenetic mechanisms that regulateBDNFexpression and function with relevance to major depressive disorder. American Journal of Medical Genetics Part B Neuropsychiatric Genetics, 177(2), 143–167. https://doi.org/10.1002/ajmg.b.32616
Ho, P. T. B., Clark, I. M., & Le, L. T. T. (2022). MicroRNA-based diagnosis and therapy. International Journal of Molecular Sciences, 23(13), 7167. https://doi.org/10.3390/ijms23137167
Huan, Z., Mei, Z., Na, H., Xinxin, M., Yaping, W., Ling, L., Lei, W., Kejin, Z., & Yanan, L. (2021). LncRNA miR-155-HG alleviates depression-like behaviors in mice by regulating the miR-155/BDNF axis. Neurochemical Research, 46(4), 935–944. https://doi.org/10.1007/s11064-021-03234-z
Huang, P., Wei, S., Luo, M., Tang, Z., Lin, Q., Wang, X., Luo, M., He, Y., Wang, C., Wei, D., Xia, C., & Xu, J. (2021). MiR-139-5p has an antidepressant-like effect by targeting phosphodiesterase 4D to activate the cAMP/PKA/CREB signaling pathway. Annals of Translational Medicine, 9(20), 1594. https://doi.org/10.21037/atm-21-5149
Institute for Quality and Efficiency in Health Care (IQWiG). (2024, April 15). Depression: Learn More – How is depression treated? InformedHealth.org - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK279282/
Issler, O., & Chen, A. (2015). Determining the role of microRNAs in psychiatric disorders. Nature Reviews Neuroscience, 16(4), 201–212. https://doi.org/10.1038/nrn3879
Issler, O., Haramati, S., Paul, E. D., Maeno, H., Navon, I., Zwang, R., Gil, S., Mayberg, H. S., Dunlop, B. W., Menke, A., Awatramani, R., Binder, E. B., Deneris, E. S., Lowry, C. A., & Chen, A. (2014). MicroRNA 135 is essential for chronic stress resiliency, antidepressant efficacy, and intact serotonergic activity. Neuron, 83(2), 344–360. https://doi.org/10.1016/j.neuron.2014.05.042
Ji, L., Ye, Y., Nie, P., Peng, J., Fu, C., Wang, Z., & Tong, L. (2019). Dysregulation of miR-142 results in anxiety-like behaviors following single prolonged stress. Behavioural Brain Research, 365, 157–163. https://doi.org/10.1016/j.bbr.2019.03.018
Karege, F., Bondolfi, G., Gervasoni, N., Schwald, M., Aubry, J., & Bertschy, G. (2005). Low brain-derived neurotrophic factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity. Biological Psychiatry, 57(9), 1068–1072. https://doi.org/10.1016/j.biopsych.2005.01.008
Kennis, M., Gerritsen, L., Van Dalen, M., Williams, A., Cuijpers, P., & Bockting, C. (2020). Prospective biomarkers of major depressive disorder: a systematic review and meta-analysis. Molecular Psychiatry, 25(2), 321–338. https://doi.org/10.1038/s41380-019-0585-z
Kim, H., Kim, J., Lee, H., Shin, E., Kang, H., Jeon, J., & Youn, B. (2021). Baiap3 regulates depressive behaviors in mice via attenuating dense core vesicle trafficking in subsets of prefrontal cortex neurons. Neurobiology of Stress, 16, 100423. https://doi.org/10.1016/j.ynstr.2021.100423
Kozomara, A., Birgaoanu, M., & Griffiths-Jones, S. (2019). miRBase: from microRNA sequences to function. Nucleic Acids Research, 47(D1), D155–D162. https://doi.org/10.1093/nar/gky1141
Kronenberg, G., Kirste, I., Inta, D., Chourbaji, S., Heuser, I., Endres, M., & Gass, P. (2009). Reduced hippocampal neurogenesis in the GR+/− genetic mouse model of depression. European Archives of Psychiatry and Clinical Neuroscience, 259(8), 499–504. https://doi.org/10.1007/s00406-009-0036-y
Kuang, W., Dong, Z., Tian, L., & Li, J. (2018). MicroRNA-451a, microRNA-34a-5p, and microRNA-221-3p as predictors of response to antidepressant treatment. Brazilian Journal of Medical and Biological Research, 51(7), e7212. https://doi.org/10.1590/1414-431x20187212
Kunugi, H., Hori, H., Adachi, N., & Numakawa, T. (2010). Interface between hypothalamic‐pituitary‐adrenal axis and brain‐derived neurotrophic factor in depression. Psychiatry and Clinical Neurosciences, 64(5), 447–459. https://doi.org/10.1111/j.1440-1819.2010.02135.x
Leal, G., Bramham, C., & Duarte, C. (2017). BDNF and hippocampal synaptic plasticity. Vitamins and Hormones, 104, 153–195. https://doi.org/10.1016/bs.vh.2016.10.004
Lee, R., Kermani, P., Teng, K. K., & Hempstead, B. L. (2001). Regulation of cell survival by secreted proneurotrophins. Science, 294(5548), 1945–1948. https://doi.org/10.1126/science.1065057
Leitão, A. L., & Enguita, F. J. (2022). A structural view of miRNA biogenesis and function. Non-coding RNA, 8(1), 10. https://doi.org/10.3390/ncrna8010010
Li, C., Wang, F., Miao, P., Yan, L., Liu, S., Wang, X., Jin, Z., & Gu, Z. (2020a). MiR-138 increases depressive-like behaviors by targeting SIRT1 in hippocampus. Neuropsychiatric Disease and Treatment, 16, 949–957. https://doi.org/10.2147/ndt.s237558
Li, S., Ma, H., Yuan, X., Zhou, X., Wan, Y., & Chen, S. (2020b). MicroRNA-382-5p targets nuclear receptor subfamily 3 group c member 1 to regulate depressive-like behaviors induced by chronic unpredictable mild stress in rats. Neuropsychiatric Disease and Treatment, 16, 2053–2061. https://doi.org/10.2147/ndt.s243920
Li, Y., Xu, M., Gao, Z., Wang, Y., Yue, Z., Zhang, Y., Li, X., Zhang, C., Xie, S., & Wang, P. (2013). Alterations of serum levels of BDNF-related miRNAs in patients with depression. PLoS ONE, 8(5), e63648. https://doi.org/10.1371/journal.pone.0063648
Li, Y., Li, S., Yan, J., Wang, D., Yin, R., Zhao, L., Zhu, Y., & Zhu, X. (2016). MiR-182 (microRNA-182) suppression in the hippocampus evokes antidepressant-like effects in rats. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 65, 96–103. https://doi.org/10.1016/j.pnpbp.2015.09.004
Li, Y., Lu, X., Nie, J., Hu, P., Ge, F., Yuan, T., & Guan, X. (2020c). MicroRNA134 of ventral hippocampus is involved in cocaine Extinction-Induced anxiety-like and depression-like behaviors in mice. Molecular Therapy — Nucleic Acids, 19, 937–950. https://doi.org/10.1016/j.omtn.2019.12.030
Li, Y., Wang, N., Pan, J., Wang, X., Zhao, Y., & Guo, Z. (2021). Hippocampal mIRNA-144 modulates depressive-like behaviors in rats by targeting PTP1B. Neuropsychiatric Disease and Treatment, 17, 389–399. https://doi.org/10.2147/ndt.s263079
Lian, N., Niu, Q., Lei, Y., Li, X., Li, Y., & Song, X. (2018). MiR-221 is involved in depression by regulating Wnt2/CREB/BDNF axis in hippocampal neurons. Cell Cycle, 17(24), 2745–2755. https://doi.org/10.1080/15384101.2018.1556060
Licursi, V., Conte, F., Fiscon, G., & Paci, P. (2019). MIENTURNET: an interactive web tool for microRNA-target enrichment and network-based analysis. BMC Bioinformatics, 20(1), 545. https://doi.org/10.1186/s12859-019-3105-x
Lin, C. C., Lee, C. T., Sun, M. H., & Huang, T. L. (2017). Increased Levels of miR-30e, miR-132, miR-185, and miR- 212 at Baseline and Increased Brain-derived Neurotrophic Factor Protein and mRNA Levels after Treatment in Patients with Major Depressive Disorder. Neuropsychiatry, 07(06), 920-926. https://doi.org/10.4172/neuropsychiatry.1000297
Liu, Y., Yang, X., Zhao, L., Zhang, J., Li, T., & Ma, X. (2016). Increased miR-132 level is associated with visual memory dysfunction in patients with depression. Neuropsychiatric Disease and Treatment, 12, 2905–2911. https://doi.org/10.2147/ndt.s116287
Liu, Z., Yang, J., Fang, Q., Shao, H., Yang, D., Sun, J., & Gao, L. (2021). MiRNA‐199a‐5p targets WNT2 to regulate depression through the CREB/BDNF signaling in hippocampal neuron. Brain and Behavior, 11(8), e02107. https://doi.org/10.1002/brb3.2107
Lopez, J. P., Lim, R., Cruceanu, C., Crapper, L., Fasano, C., Labonte, B., Maussion, G., Yang, J. P., Yerko, V., Vigneault, E., Mestikawy, S. E., 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), 764–768. https://doi.org/10.1038/nm.3582
Marwaha, S., Palmer, E., Suppes, T., Cons, E., Young, A. H., & Upthegrove, R. (2023). Novel and emerging treatments for major depression. The Lancet, 401(10371), 141–153. https://doi.org/10.1016/s0140-6736(22)02080-3
Miao, Z., Mao, F., Liang, J., Szyf, M., Wang, Y., & Sun, Z. S. (2018). Anxiety-related behaviours associated with microRNA-206-3p and BDNF expression in pregnant female mice following psychological social stress. Molecular Neurobiology, 55(2), 1097–1111. https://doi.org/10.1007/s12035-016-0378-1
Mikulska, J., Juszczyk, G., Gawrońska-Grzywacz, M., & Herbet, M. (2021). HPA axis in the pathomechanism of depression and schizophrenia: new therapeutic strategies based on its participation. Brain Sciences, 11(10), 1298. https://doi.org/10.3390/brainsci11101298
Miranda, M., Morici, J. F., Zanoni, M. B., & Bekinschtein, P. (2019). Brain-Derived neurotrophic factor: a key molecule for memory in the healthy and the pathological brain. Frontiers in Cellular Neuroscience, 13, 363. https://doi.org/10.3389/fncel.2019.00363
Moliner, R., Girych, M., Brunello, C. A., Kovaleva, V., Biojone, C., Enkavi, G., Antenucci, L., Kot, E. F., Goncharuk, S. A., Kaurinkoski, K., Kuutti, M., Fred, S. M., Elsilä, L. V., Sakson, S., Cannarozzo, C., Diniz, C. R. a. F., Seiffert, N., Rubiolo, A., Haapaniemi, H., . . . Castrén, E. (2023). Psychedelics promote plasticity by directly binding to BDNF receptor TrkB. Nature Neuroscience, 26(6), 1032–1041. https://doi.org/10.1038/s41593-023-01316-5
Mowla, S. J., Farhadi, H. F., Pareek, S., Atwal, J. K., Morris, S. J., Seidah, N. G., & Murphy, R. A. (2001). Biosynthesis and post-translational processing of the precursor to brain-derived neurotrophic factor. Journal of Biological Chemistry, 276(16), 12660–12666. https://doi.org/10.1074/jbc.m008104200
Nibuya, M., Morinobu, S., & Duman, R. (1995). Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. Journal of Neuroscience, 15(11), 7539–7547. https://doi.org/10.1523/jneurosci.15-11-07539.1995
Ortega, M. A., Alvarez-Mon, M. A., García-Montero, C., Fraile-Martinez, O., Lahera, G., Monserrat, J., Muñoz-Merida, L., Mora, F., Rodríguez-Jiménez, R., Fernandez-Rojo, S., Quintero, J., & Álvarez-Mon, M. (2021). MicroRNAs as critical biomarkers of major depressive disorder: A comprehensive perspective. Biomedicines, 9(11), 1659. https://doi.org/10.3390/biomedicines9111659
Pang, P. T., Teng, H. K., Zaitsev, E., Woo, N. T., Sakata, K., Zhen, S., Teng, K. K., Yung, W., Hempstead, B. L., & Lu, B. (2004). Cleavage of proBDNF by TPA/plasmin is essential for long-term hippocampal plasticity. Science, 306(5695), 487–491. https://doi.org/10.1126/science.1100135
Porter, G. A., & O’Connor, J. C. (2022). Brain-derived neurotrophic factor and inflammation in depression: pathogenic partners in crime? World Journal of Psychiatry, 12(1), 77–97. https://doi.org/10.5498/wjp.v12.i1.77
Qi, S., Yang, X., Zhao, L., Calhoun, V. D., Perrone-Bizzozero, N., Liu, S., Jiang, R., Jiang, T., Sui, J., & Ma, X. (2018). MicroRNA132 associated multimodal neuroimaging patterns in unmedicated major depressive disorder. Brain, 141(3), 916–926. https://doi.org/10.1093/brain/awx366
Rajasethupathy, P., Fiumara, F., Sheridan, R., Betel, D., Puthanveettil, S. V., Russo, J. J., Sander, C., Tuschl, T., & Kandel, E. (2009). Characterization of small RNAs in aplysia reveals a role for miR-124 in constraining synaptic plasticity through CREB. Neuron, 63(6), 803–817. https://doi.org/10.1016/j.neuron.2009.05.029
Roy, B., Dunbar, M., Agrawal, J., Allen, L., & Dwivedi, Y. (2020). Amygdala-based altered MIRNome and epigenetic contribution of MIR-128-3P in conferring susceptibility to depression-like behavior via WNT signaling. The International Journal of Neuropsychopharmacology, 23(3), 165–177. https://doi.org/10.1093/ijnp/pyz071
Roy, B., Dunbar, M., Shelton, R. C., & Dwivedi, Y. (2017). Identification of microRNA-124-3P as a putative epigenetic signature of major depressive disorder. Neuropsychopharmacology, 42(4), 864–875. https://doi.org/10.1038/npp.2016.175
Schmidt, M. V., Sterlemann, V., Wagner, K., Niederleitner, B., Ganea, K., Liebl, C., Deussing, J. M., Berger, S., SchüTz, G., Holsboer, F., & MüLler, M. B. (2009). Postnatal glucocorticoid excess due to pituitary glucocorticoid receptor deficiency: differential short- and long-term consequences. Endocrinology, 150(6), 2709–2716. https://doi.org/10.1210/en.2008-1211
Schwarzenbach, H., Nishida, N., Calin, G. A., & Pantel, K. (2014). Clinical relevance of circulating cell-free microRNAs in cancer. Nature Reviews Clinical Oncology, 11(3), 145–156. https://doi.org/10.1038/nrclinonc.2014.5
Seyhan, A. A. (2024). Trials and tribulations of microRNA therapeutics. International Journal of Molecular Sciences, 25(3), 1469. https://doi.org/10.3390/ijms25031469
Shen, J., Li, Y., Qu, C., Xu, L., Sun, H., & Zhang, J. (2019). The enriched environment ameliorates chronic unpredictable mild stress-induced depressive-like behaviors and cognitive impairment by activating the SIRT1/miR-134 signaling pathway in hippocampus. Journal of Affective Disorders, 248, 81–90. https://doi.org/10.1016/j.jad.2019.01.031
Shen, J., Xu, L., Qu, C., Sun, H., & Zhang, J. (2018). Resveratrol prevents cognitive deficits induced by chronic unpredictable mild stress: Sirt1/miR-134 signalling pathway regulates CREB/BDNF expression in hippocampus in vivo and in vitro. Behavioural Brain Research, 349, 1–7. https://doi.org/10.1016/j.bbr.2018.04.050
Shi, L., Ji, C., Tang, W., Liu, Y., Zhang, W., & Guan, W. (2022). Hippocampal miR-124 participates in the pathogenesis of depression via regulating the expression of BDNF in a chronic social defeat stress model of depression. Current Neurovascular Research, 19(2), 210–218. https://doi.org/10.2174/1567202619666220713105306
Su, B., Cheng, S., Wang, L., & Wang, B. (2022). MicroRNA-139-5p acts as a suppressor gene for depression by targeting nuclear receptor subfamily 3, group C, member 1. Bioengineered, 13(5), 11856–11866. https://doi.org/10.1080/21655979.2022.2059937
Su, M., Hong, J., Zhao, Y., Liu, S., & Xue, X. (2015). MeCP2 controls hippocampal brain-derived neurotrophic factor expression via homeostatic interactions with microRNA-132 in rats with depression. Molecular Medicine Reports, 12(4), 5399–5406. https://doi.org/10.3892/mmr.2015.4104
Sun, P., Liu, D. Z., Jickling, G. C., Sharp, F. R., & Yin, K. (2018). MicroRNA-based therapeutics in central nervous system injuries. Journal of Cerebral Blood Flow & Metabolism, 38(7), 1125–1148. https://doi.org/10.1177/0271678x18773871
Tan, P., Xue, T., Wang, Y., Hu, Z., Su, J., Yang, R., Ji, J., Ye, M., Chen, Z., Huang, C., & Lu, X. (2022). Hippocampal NR6A1 impairs CREB-BDNF signaling and leads to the development of depression-like behaviors in mice. Neuropharmacology, 209, 108990. https://doi.org/10.1016/j.neuropharm.2022.108990
Tang, Y., Yang, J., Ye, C., Xu, X., Cai, M., Zhang, Y., Lu, H., Mo, F., Li, H., & Shen, H. (2022). miR-182 mediated the inhibitory effects of NF-κB on the GPR39/CREB/BDNF pathway in the hippocampus of mice with depressive-like behaviors. Behavioural Brain Research, 418, 113647. https://doi.org/10.1016/j.bbr.2021.113647
Tong, L., Li, M., Nie, P., Chen, Y., Chen, Y., & Ji, L. (2021). 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. Neurobiology of Stress, 14, 100311. https://doi.org/10.1016/j.ynstr.2021.100311
Treiber, T., Treiber, N., & Meister, G. (2018). Author correction: regulation of microRNA biogenesis and its crosstalk with other cellular pathways. Nature Reviews Molecular Cell Biology, 19(12), 808. https://doi.org/10.1038/s41580-018-0070-6
Uchida, S., Nishida, A., Hara, K., Kamemoto, T., Suetsugi, M., Fujimoto, M., Watanuki, T., Wakabayashi, Y., Otsuki, K., McEwen, B. S., & Watanabe, Y. (2008). Characterization of the vulnerability to repeated stress in Fischer 344 rats: possible involvement of microRNA‐mediated down‐regulation of the glucocorticoid receptor. European Journal of Neuroscience, 27(9), 2250–2261. https://doi.org/10.1111/j.1460-9568.2008.06218.x
Voleti, B., & Duman, R. S. (2012). The roles of neurotrophic factor and WNT signaling in depression. Clinical Pharmacology & Therapeutics, 91(2), 333–338. https://doi.org/10.1038/clpt.2011.296
Vreugdenhil, E., Verissimo, C. S. L., Mariman, R., Kamphorst, J. T., Barbosa, J. S., Zweers, T., Champagne, D. L., Schouten, T., Meijer, O. C., De Kloet, E. R., & Fitzsimons, C. P. (2009). MicroRNA 18 and 124a Down-Regulate the glucocorticoid receptor: implications for glucocorticoid responsiveness in the brain. Endocrinology, 150(5), 2220–2228. https://doi.org/10.1210/en.2008-1335
Wang, G., An, T., Lei, C., Zhu, X., Yang, L., Zhang, L., & Zhang, R. (2022). Antidepressant-like effect of ginsenoside Rb1 on potentiating synaptic plasticity via the miR-134–mediated BDNF signaling pathway in a mouse model of chronic stress-induced depression. Journal of Ginseng Research, 46(3), 376–386. https://doi.org/10.1016/j.jgr.2021.03.005
Wang, Q., Zhao, G., Yang, Z., Liu, X., & Xie, P. (2018). Downregulation of microRNA 124 3p suppresses the mTOR signaling pathway by targeting DDIT4 in males with major depressive disorder. International Journal of Molecular Medicine, 41, 493–500. https://doi.org/10.3892/ijmm.2017.3235
Wang, S., Mu, R., Li, C., Dong, S., Geng, D., Liu, Q., & Yi, L. (2017). MicroRNA-124 targets glucocorticoid receptor and is involved in depression-like behaviors. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 79, 417–425. https://doi.org/10.1016/j.pnpbp.2017.07.024
Weaver, D. T., Pishas, K. I., Williamson, D., Scarborough, J., Lessnick, S. L., Dhawan, A., & Scott, J. G. (2021). Network potential identifies therapeutic miRNA cocktails in Ewing sarcoma. PLoS Computational Biology, 17(10), e1008755. https://doi.org/10.1371/journal.pcbi.1008755
World Health Organization. (2023, December 7). Depressive disorder (depression). Knowledge Action Portal. https://www.knowledge-action-portal.com/en/content/depressive-disorder-depression
Xian, X., Cai, L., Li, Y., Wang, R., Xu, Y., Chen, Y., Xie, Y., Zhu, X., & Li, Y. (2022). Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression. Journal of Nanobiotechnology, 20(1), 122. https://doi.org/10.1186/s12951-022-01332-w
Xu, B., Wang, T., Xiao, J., Dong, W., Wen, H., Wang, X., Qin, Y., Cai, N., Zhou, Z., Xu, J., & Wang, H. (2019). FCPR03, a novel phosphodiesterase 4 inhibitor, alleviates cerebral ischemia/reperfusion injury through activation of the AKT/GSK3β/ β-catenin signaling pathway. Biochemical Pharmacology, 163, 234–249. https://doi.org/10.1016/j.bcp.2019.02.023
Xu, N., Meng, H., Liu, T., Feng, Y., Qi, Y., Zhang, D., & Wang, H. (2017). Blueberry phenolics reduce gastrointestinal infection of patients with cerebral venous thrombosis by improving depressant-induced autoimmune disorder via miR-155-mediated brain-derived neurotrophic factor. Frontiers in Pharmacology, 8, 853. https://doi.org/10.3389/fphar.2017.00853
Yang, T., Nie, Z., Shu, H., Kuang, Y., Chen, X., Cheng, J., Yu, S., & Liu, H. (2020a). The role of BDNF on neural plasticity in depression. Frontiers in Cellular Neuroscience, 14, 82. https://doi.org/10.3389/fncel.2020.00082
Yang, W., Liu, M., Zhang, Q., Zhang, J., Chen, J., Chen, Q., & Suo, L. (2020b). Knockdown of miR-124 reduces depression-like behavior by targeting CREB1 and BDNF. Current Neurovascular Research, 17(2), 196–203. https://doi.org/10.2174/1567202617666200319141755
Yang, X., Yang, Q., Wang, X., Luo, C., Wan, Y., Li, J., Liu, K., Zhou, M., & Zhang, C. (2014). MicroRNA expression profile and functional analysis reveal that miR-206 is a critical novel gene for the expression of BDNF induced by ketamine. NeuroMolecular Medicine, 16(3), 594–605. https://doi.org/10.1007/s12017-014-8312-z
Yu, H., Fan, C., Yang, L., Yu, S., Song, Q., Wang, P., & Mao, X. (2018). Ginsenoside RG1 prevents chronic Stress-Induced Depression-Like behaviors and neuronal structural plasticity in rats. Cellular Physiology and Biochemistry, 48(6), 2470–2482. https://doi.org/10.1159/000492684
Zhang, X., Xue, Y., Li, J., Xu, H., Yan, W., Zhao, Z., Yu, W., Zhai, X., Sun, Y., Wu, Y., Li, Y., Gui, L., Yu, D., Xiao, Z., & Yin, S. (2021a). The involvement of ADAR1 in antidepressant action by regulating BDNF via miR-432. Behavioural Brain Research, 402, 113087. https://doi.org/10.1016/j.bbr.2020.113087
Zhang, X., Yan, W., Xue, Y., Xu, H., Li, J., Zhao, Z., Sun, Y., Wang, Y., He, J., Huang, Y., Yu, D., Xiao, Z., & Yin, S. (2021b). Roles of miR-432 and circ_0000418 in mediating the anti-depressant action of ADAR1. Neurobiology of Stress, 15, 100396. https://doi.org/10.1016/j.ynstr.2021.100396
Zhang, Z., Xia, D., & Xu, A. (2022). Therapeutic effect of fastigial nucleus stimulation is mediated by the microRNA-182 & microRNA-382/BDNF signaling pathways in the treatment of post-stroke depression. Biochemical and Biophysical Research Communications, 627, 137–145. https://doi.org/10.1016/j.bbrc.2022.05.038
Zhao, Y., Wang, S., Chu, Z., Dang, Y., Zhu, J., & Su, X. (2017). MicroRNA-101 in the ventrolateral orbital cortex (VLO) modulates depressive-like behaviors in rats and targets dual-specificity phosphatase 1 (DUSP1). Brain Research, 1669, 55–62. https://doi.org/10.1016/j.brainres.2017.05.020
Zheng, Y., Sheng, X., Jin, X., & Guan, W. (2024). MIR-182-5P: A novel biomarker in the treatment of depression in CSDS-Induced mice. The International Journal of Neuropsychopharmacology, 27(1), pyad064. https://doi.org/10.1093/ijnp/pyad064
Zou, Z., Chen, J., Feng, H., Cheng, Y., Wang, H., Zhou, Z., Guo, H., Zheng, W., & Xu, J. (2017). Novel phosphodiesterase 4 inhibitor FCPR03 alleviates Lipopolysaccharide-Induced neuroinflammation by regulation of the CAMP/PKA/CREB signaling pathway and NF-ΚB inhibition. Journal of Pharmacology and Experimental Therapeutics, 362(1), 67–77. https://doi.org/10.1124/jpet.116.239608
Żurawek, D., & Turecki, G. (2021). The miRNome of depression. International Journal of Molecular Sciences, 22(21), 11312. https://doi.org/10.3390/ijms222111312
Downloads
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2025 Thi Minh Thu Nguyen, Si Bao Nguyen, Thi Thu Hang Do
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The observations and associated materials published or posted by NeurosciRN are licensed by the authors for use and distribution in accord with the Creative Commons Attribution license CC BY-NC 4.0 international, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
