miR-206 regulates brain-derived neurotrophic factor in Alzheimer disease model
Abstract
Objective: Alzheimer disease (AD) brains are deficient in brain‐derived neurotrophic factor (BDNF), which regulates synaptic plasticity and memory. MicroRNAs (miRNAs) are ∼22‐nucleotide small noncoding RNAs that control a variety of physiological and disease processes. Here, we show that miR‐206 regulates BDNF and memory function in AD mice. Methods: Expression of miRNAs was analyzed in Tg2576 AD transgenic mice and human AD brain samples. Regulation of BDNF by a selected miRNA was validated by in silico prediction, target gene luciferase assay, and dendritic spine responses in neurons. AM206, a neutralizing inhibitor of miR‐206 (antagomir), was injected into the third ventricle of Tg2576 mice, after which memory function, synaptogenesis, neurogenesis, and target gene expression were assessed. For noninvasive delivery, antagomirs were administered intranasally. Results: The brains of Tg2576 mice and the temporal cortex of human AD brains had increased levels of miR‐206. This miRNA targeted BDNF transcripts, and AM206 prevented the detrimental effects of amyloid‐β42 on BDNF and dendritic spine degeneration in Tg2576 neurons. Injection of AM206 into the cerebral ventricles of AD mice increased the brain levels of BDNF and improved their memory function. In parallel, AM206 enhanced the hippocampal synaptic density and neurogenesis. Furthermore, intranasally administered AM206 also reached the brain and increased BDNF levels and memory function in AD mice. Interpretation: Our findings demonstrate a novel miRNA‐dependent regulation of BDNF in AD and suggest possible therapeutic approaches, such as noninvasive intranasal delivery of AM206. ANN NEUROL 2012;72:269–277.
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MiR-206 is consistently elevated in AD cortex and serum, suppresses BDNF and IGF1, and is associated with synaptic decline and cognitive deficits.
“MiR-206 is consistently elevated in AD cortex and serum, suppresses BDNF and IGF1, and is associated with synaptic decline and cognitive deficits (Lee et al., 2012; Tian et al., 2014).”
From Cell-specific MicroRNA networks orchestrate the pathogenesis of Alzheimer’s disease (2026) · cites this paper as Lee et al., 2012
Elevated levels of miR-206, miR-34a, miR-125b, and let-7b in plasma or CSF reflect trophic withdrawal, apoptosis, and innate immune activation.
“Elevated levels of miR-206, miR-34a, miR-125b, and let-7b in plasma or CSF reflect trophic withdrawal, apoptosis, and innate immune activation, highlighting their pathogenic roles in neuronal and glial cells, though cohort replication varies (Banzhaf-Strathmann et al., 2014; Lee et al., 2012; Lehmann et al., 2012; Riancho et al., 2017; Sarkar et al., 2016; Tian et al., 2014).”
From Cell-specific MicroRNA networks orchestrate the pathogenesis of Alzheimer’s disease (2026) · cites this paper as Lee et al., 2012
Cites
Querfurth, H. W., & LaFerla, F. M. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0909142 · Cited by 4,569 · see citing works
Cogswell, J. P., Ward, J., Taylor, I. A., Waters, M., Shi, Y., Cannon, B., Kelnar, K., Kemppainen, J., Brown, D., Chen, C., et al. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-14103 · Cited by 943 · see citing works
Packer, A. N., Xing, Y., Harper, S. Q., Jones, L., & Davidson, B. L. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.2390-08.2008 · Cited by 679 · see citing works
SZE, C.-I., TRONCOSO, J. C., KAWAS, C., MOUTION, P., PRICE, D. L., & MARTIN, L. J. (1997) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199708000-00011 · Cited by 562 · see citing works
Alterations of the microRNA network cause neurodegenerative disease
Hébert, S. S., & De Strooper, B. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2008.12.003 · Cited by 452 · see citing works
Wang, X., Liu, P., Zhu, H., Xu, Y., Ma, C., Dai, X., Huang, L., Liu, Y., Zhang, L., & Qin, C. (2009) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2009.08.006 · Cited by 271 · see citing works
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Serum Brain-Derived Neurotrophic Factor and the Risk for Dementia: The Framingham Heart Study
Weinstein, G., Beiser, A. S., Choi, S. H., Preis, S. R., Chen, T. C., Vorgas, D., Au, R., Pikula, A., Wolf, P. A., DeStefano, A. L., et al. (2014) · JAMA Neurology · doi:10.1001/jamaneurol.2013.4781 · Cited by 289 · see citing works
Antisense oligonucleotides: translation from mouse models to human neurodegenerative diseases
Schoch, K. M., & Miller, T. M. (2017) · Neuron · doi:10.1016/j.neuron.2017.04.010 · Cited by 274 · see citing works
“Similar results were seen with intranasal delivery (Lee et al., 2012), highlighting this method as a possible noninvasive delivery route for ASOs.”
Advances in the development of new biomarkers for Alzheimer’s disease
Klyucherev, T. O., Olszewski, P., Shalimova, A. A., Chubarev, V. N., Tarasov, V. V., Attwood, M. M., Syvänen, S., & Schiöth, H. B. (2022) · Translational Neurodegeneration · doi:10.1186/s40035-022-00296-z · Cited by 241 · see citing works
Method for widespread microRNA-155 inhibition prolongs survival in ALS-model mice
Koval, E. D., Shaner, C., Zhang, P., du Maine, X., Fischer, K., Tay, J., Chau, B. N., Wu, G. F., & Miller, T. M. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt261 · Cited by 236 · see citing works
Role of BDNF epigenetics in activity-dependent neuronal plasticity
Karpova, N. N. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.04.002 · Cited by 200 · see citing works
Microbial regulation of microRNA expression in the amygdala and prefrontal cortex
Hoban, A. E., Stilling, R. M., M. Moloney, G., Moloney, R. D., Shanahan, F., Dinan, T. G., Cryan, J. F., & Clarke, G. (2017) · Microbiome · doi:10.1186/s40168-017-0321-3 · Cited by 177 · see citing works
Antisense oligonucleotides: treating neurodegeneration at the level of RNA
DeVos, S. L., & Miller, T. M. (2013) · Neurotherapeutics · doi:10.1007/s13311-013-0194-5 · Cited by 164 · see citing works
BDNF Val66Met, Aβ amyloid, and cognitive decline in preclinical Alzheimer's disease
Lim, Y. Y., Villemagne, V. L., Laws, S. M., Ames, D., Pietrzak, R. H., Ellis, K. A., Harrington, K. D., Bourgeat, P., Salvado, O., Darby, D., et al. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.05.006 · Cited by 124 · see citing works
Lim, Y. Y., Villemagne, V. L., Laws, S. M., Ames, D., Pietrzak, R. H., Ellis, K. A., Harrington, K., Bourgeat, P., Bush, A. I., Martins, R. N., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0086498 · Cited by 110 · see citing works
Epigenetic memory: The Lamarckian brain
Fischer, A. (2014) · The EMBO Journal · doi:10.1002/embj.201387637 · Cited by 107 · see citing works
Lim, Y. Y., Hassenstab, J., Cruchaga, C., Goate, A., Fagan, A. M., Benzinger, T. L. S., Maruff, P., Snyder, P. J., Masters, C. L., Allegri, R., et al. (2016) · Brain · doi:10.1093/brain/aww200 · Cited by 76 · see citing works
Early diagnosis of Alzheimer's disease from elevated olfactory mucosal miR-206 level.
Moon, J., Lee, S.-T., Kong, I. G., Byun, J.-I., Sunwoo, J.-S., Shin, J.-W., Shim, J.-Y., Park, J.-H., Jeon, D., Jung, K.-H., et al. (2016) · Scientific Reports · doi:10.1038/srep20364 · Cited by 69 · see citing works
Self-citationYang, X., Yang, Q., Wang, X., Luo, C., Wan, Y., Li, J., Liu, K., Zhou, M., & Zhang, C. (2014) · NeuroMolecular Medicine · doi:10.1007/s12017-014-8312-z · Cited by 69 · see citing works
MiRNA-206 and BDNF genes interacted in bipolar I disorder.
Wang, Z., Zhang, C., Huang, J., Yuan, C., Hong, W., Chen, J., Yu, S., Xu, L., Gao, K., & Fang, Y. (2014) · Journal of Affective Disorders · doi:10.1016/j.jad.2014.03.047 · Cited by 44 · see citing works
MicroRNA-206 Regulates Stress-Provoked Aggressive Behaviors in Post-weaning Social Isolation Mice.
Chang, C.-H., Kuek, E. J. W., Su, C.-L., & Gean, P.-W. (2020) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2020.05.001 · Cited by 35 · see citing works
Li, X., Zhao, J., Li, Z., Zhang, L., & Huo, Z. (2020) · Neural Plasticity · doi:10.1155/2020/8850653 · Cited by 35 · see citing works
Potential Roles of microRNAs in the Regulation of Monoamine Oxidase A in the Brain
Higuchi, Y., Soga, T., & Parhar, I. S. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00339 · Cited by 22 · see citing works
Weinstein, G., Preis, S. R., Beiser, A. S., Kaess, B., Chen, T. C., Satizabal, C., Rahman, F., Benjamin, E. J., Vasan, R. S., & Seshadri, S. (2017) · Current Alzheimer Research · doi:10.2174/1567205014666170203094520 · Cited by 17 · see citing works
Cell-specific MicroRNA networks orchestrate the pathogenesis of Alzheimer’s disease
Donepudi, K., Eadha, S., Rodarte, D., Sharma, B., & Kumar, S. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103211
- Authors
- Lee, S., Chu, K., Jung, K., Kim, J. H., Huh, J., Yoon, H., Park, D., Lim, J., Kim, J., Jeon, D., Ryu, H., Lee, S. K., Kim, M., & Roh, J.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2012-08
- Volume
- 72
- Issue
- 2
- Pages
- 269-277
- ISSN
- 0364-5134
- 1531-8249
- Cited by
- 275
- References
- 6
- Language
- en
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