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microRNAs in Normal Brain Physiology

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IschemiRs: MicroRNAs in Ischemic Stroke

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Abstract

MicroRNAs (miRs) are short single-stranded non-coding RNAs that regulate protein synthesis by translational repression or degradation by targeting mRNAs at the post-transcriptional level. Highly conserved across species, they are known to regulate many genes in critical pathways during the lifetime. Any dysregulation at the cellular level, but also in the entire organism, is therefore harmful. The brain is a privileged organ in many ways, and interestingly, the majority of miRs are expressed in the brain. We describe miRs biogenesis in this chapter and focus on the role of cell-specific miRs in normal brain physiology and homeostasis.

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References

  1. Ambros V (2004) The functions of animal microRNAs. Nature 431(7006):350–355

    Article  CAS  PubMed  Google Scholar 

  2. Christensen M, Schratt GM (2009) microRNA involvement in developmental and functional aspects of the nervous system and in neurological diseases. Neurosci Lett 466(2):55–62

    Article  CAS  PubMed  Google Scholar 

  3. Sayed D, Abdellatif M (2011) MicroRNAs in development and disease. Physiol Rev 91(3):827–887

    Article  CAS  PubMed  Google Scholar 

  4. Gaetano S (ed) (2015) microRNA: medical evidence: from molecular biology to clinical practice. Springer, Cham. https://doi.org/10.1007/978-3-319-22671-2

    Book  Google Scholar 

  5. Eyileten C, Wicik Z, De Rosa S, Mirowska-Guzel D, Soplinska A, Indolfi C, Jastrzebska-Kurkowska I, Czlonkowska A, Postula M (2018) MicroRNAs as diagnostic and prognostic biomarkers in ischemic stroke-A comprehensive review and bioinformatic analysis. Cell 7(12):E249

    Article  CAS  Google Scholar 

  6. Wang SW, Liu Z, Shi ZS (2018) Non-coding RNA in acute ischemic stroke: mechanisms, biomarkers and therapeutic targets. Cell Transplant 27(12):1763–1777

    Article  PubMed  PubMed Central  Google Scholar 

  7. Kozomara A, Birgaoanu M, Griffiths-Jones S (2019) miRBase: from microRNA sequences to function. Nucleic Acids Res 47(D1):D155–D162

    Article  CAS  PubMed  Google Scholar 

  8. Ul HM (2012) Micro-RNAs (miRNAs): genomic organisation, biogenesis and mode of action. Cell Tissue Res 349(2):405–413

    Article  CAS  Google Scholar 

  9. Adlakha YK, Saini N (2014) Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128. Mol Cancer 13:33

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A (2004) Identification of mammalian microRNA host genes and transcription units. Genome Res 14(10A):1902–1910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Stavast CJ, Erkeland SJ (2019) The non-canonical aspects of MicroRNAs: many roads to gene regulation. Cell 8(11):E1465

    Article  CAS  Google Scholar 

  12. Ha M, Kim VN (2014) Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol 15(8):509–524

    Article  CAS  PubMed  Google Scholar 

  13. Nowak JS, Michlewski G (2013) miRNAs in development and pathogenesis of the nervous system. Biochem Soc Trans 41(4):815–820

    Article  CAS  PubMed  Google Scholar 

  14. Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V (2004) Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol 5(3):R13

    Article  PubMed  PubMed Central  Google Scholar 

  15. Jovičić A, Roshan R, Moisoi N, Pradervand S, Moser R, Pillai B, Luthi-Carter R (2013) Comprehensive expression analyses of neural cell-type-specific miRNAs identify new determinants of the specification and maintenance of neuronal phenotypes. J Neurosci 33(12):5127–5137

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Nampoothiri SS, Rajanikant GK (2017) Decoding the ubiquitous role of microRNAs in neurogenesis. Mol Neurobiol 54(3):2003–2011

    Article  CAS  PubMed  Google Scholar 

  17. Vieira MS, Santos AK, Vasconcellos R, Goulart VAM, Parreira RC, Kihara AH, Ulrich H, Resende RR (2018) Neural stem cell differentiation into mature neurons: mechanisms of regulation and biotechnological applications. Biotechnol Adv 36(7):1946–1970

    Article  CAS  PubMed  Google Scholar 

  18. Coolen M, Katz S, Bally-Cuif L (2013) miR-9: a versatile regulator of neurogenesis. Front Cell Neurosci 7:220

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Dajas-Bailador F, Bonev B, Garcez P, Stanley P, Guillemot F, Papalopulu N (2012) microRNA-9 regulates axon extension and branching by targeting Map 1b in mouse cortical neurons. Nat Neurosci 15(5):697–699

    Article  CAS  PubMed  Google Scholar 

  20. Krichevsky AM, Sonntag KC, Isacson O, Kosik KS (2006) Specific microRNAs modulate embryonic stem cell-derived neurogenesis. Stem Cells 24(4):857–864

    Article  CAS  PubMed  Google Scholar 

  21. Li G, Ling S (2017) MiR-124 promotes newborn olfactory bulb neuron dendritic morphogenesis and spine density. J Mol Neurosci 61(2):159–168

    Article  CAS  PubMed  Google Scholar 

  22. Rajasethupathy P, Fiumara F, Sheridan R, Betel D, Puthanveettil SV, Russo JJ, 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Yu JY, Chung KH, Deo M, Thompson RC, Turner DL (2008) MicroRNA miR-124 regulates neurite outgrowth during neuronal differentiation. Exp Cell Res 314(14):2618–2633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Petri R, Pircs K, Jönsson ME, Åkerblom M, Brattås PL, Klussendorf T, Jakobsson J (2017) let-7 regulates radial migration of new-born neurons through positive regulation of autophagy. EMBO J 36(10):1379–1391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhao C, Sun G, Li S, Lang MF, Yang S, Li W, Shi Y (2010) MicroRNA let-7b regulates neural stem cell proliferation and differentiation by targeting nuclear receptor TLX signaling. Proc Natl Acad Sci U S A 107(5):1876–1881

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Brett JO, Renault VM, Rafalski VA, Webb AE, Brunet A (2011) The microRNA cluster miR-106b~25 regulates adult neural stem/progenitor cell proliferation and neuronal differentiation. Aging (Albany NY) 3(2):108–124

    Article  CAS  Google Scholar 

  27. Gao J, Wang WY, Mao YW, Gräff J, Guan JS, Pan L, Mak G, Kim D, Su SC, Tsai LH (2010) A novel pathway regulates memory and plasticity via SIRT1 and miR-134. Nature 466(7310):1105–1109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Smrt RD, Szulwach KE, Pfeiffer RL, Li X, Guo W, Pathania M, Teng ZQ, Luo Y, Peng J, Bordey A, Jin P, Zhao X (2010) MicroRNA miR-137 regulates neuronal maturation by targeting ubiquitin ligase mind bomb-1. Stem Cells 28(6):1060–1070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sun G, Ye P, Murai K, Lang MF, Li S, Zhang H, Li W, Fu C, Yin J, Wang A, Ma X, Shi Y (2011) miR-137 forms a regulatory loop with nuclear receptor TLX and LSD1 in neural stem cells. Nat Commun 2:529

    Article  PubMed  CAS  Google Scholar 

  30. van Tilborg E, Heijnen CJ, Benders MJ, van Bel F, Fleiss B, Gressens P, Nijboer CH (2016) Impaired oligodendrocyte maturation in preterm infants: potential therapeutic targets. Prog Neurobiol 136:28–49

    Article  PubMed  CAS  Google Scholar 

  31. Xiao D, Qu Y, Pan L, Li X, Mu D (2018) MicroRNAs participate in the regulation of oligodendrocytes development in white matter injury. Rev Neurosci 29(2):151–160

    Article  CAS  PubMed  Google Scholar 

  32. Li JS, Yao ZX (2012) MicroRNA patents in demyelinating diseases: a new diagnostic and therapeutic perspective. Recent Pat DNA Gene Seq 6(1):47–55

    Article  CAS  PubMed  Google Scholar 

  33. Zhao X, Wu J, Zheng M, Gao F, Ju G (2012) Specification and maintenance of oligodendrocyte precursor cells from neural progenitor cells: involvement of microRNA-7a. Mol Biol Cell 23(15):2867–2878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ebrahimi-Barough S, Kouchesfehani HM, Ai J, Mahmoodinia M, Tavakol S, Massumi M (2013) Programming of human endometrial-derived stromal cells (EnSCs) into pre-oligodendrocyte cells by overexpression of miR-219. Neurosci Lett 537:65–70

    Article  CAS  PubMed  Google Scholar 

  35. Liu S, Ren C, Qu X, Wu X, Dong F, Chand YK, Fan H, Yao R, Geng D (2017) miR-219 attenuates demyelination in cuprizone-induced demyelinated mice by regulating monocarboxylate transporter 1. Eur J Neurosci 45(2):249–259

    Article  PubMed  Google Scholar 

  36. Liu XS, Chopp M, Pan WL, Wang XL, Fan BY, Zhang Y, Kassis H, Zhang RL, Zhang XM, Zhang ZG (2017) MicroRNA-146a promotes oligodendrogenesis in stroke. Mol Neurobiol 54(1):227–237

    Article  CAS  PubMed  Google Scholar 

  37. Buller B, Chopp M, Ueno Y, Zhang L, Zhang RL, Morris D, Zhang Y, Zhang ZG (2012) Regulation of serum response factor by miRNA-200 and miRNA-9 modulates oligodendrocyte progenitor cell differentiation. Glia 60(12):1906–1914

    Article  PubMed  PubMed Central  Google Scholar 

  38. Lau P, Verrier JD, Nielsen JA, Johnson KR, Notterpek L, Hudson LD (2008) Identification of dynamically regulated microRNA and mRNA networks in developing oligodendrocytes. J Neurosci 28(45):11720–11730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Dugas JC, Notterpek L (2011) MicroRNAs in oligodendrocyte and Schwann cell differentiation. Dev Neurosci 33(1):14–20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Lin ST, Fu YH (2009) miR-23 regulation of Lamin B1 is crucial for oligodendrocyte development and myelination. Dis Model Mech 2(3-4):178–188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lin ST, Heng MY, Ptáček LJ, Fu YH (2014) Regulation of myelination in the central nervous system by nuclear lamin B1 and non-coding RNAs. Transl Neurodegener 3(1):4

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Lecca D, Marangon D, Coppolino GT, Méndez AM, Finardi A, Costa GD, Martinelli V, Furlan R, Abbracchio MP (2016) MiR-125a-3p timely inhibits oligodendroglial maturation and is pathologically up-regulated in human multiple sclerosis. Sci Rep 6:34503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Lehotzky A, Lau P, Tokési N, Muja N, Hudson LD, Ovádi J (2010) Tubulin polymerization-promoting protein (TPPP/p25) is critical for oligodendrocyte differentiation. Glia 58(2):157–168

    Article  PubMed  PubMed Central  Google Scholar 

  44. Shin D, Howng SY, Ptáček LJ, Fu YH (2012) miR-32 and its target SLC45A3 regulate the lipid metabolism of oligodendrocytes and myelin. Neuroscience 213:29–37

    Article  CAS  PubMed  Google Scholar 

  45. Zhang J, Zhang ZG, Lu M, Wang X, Shang X, Elias SB, Chopp M (2017) MiR-146a promotes remyelination in a cuprizone model of demyelinating injury. Neuroscience 348:252–263

    Article  CAS  PubMed  Google Scholar 

  46. Shin D, Shin JY, McManus MT, Ptácek LJ, Fu YH (2009) Dicer ablation in oligodendrocytes provokes neuronal impairment in mice. Ann Neurol 66(6):843–857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Vasile F, Dossi E, Rouach N (2017) Human astrocytes: structure and functions in the healthy brain. Brain Struct Funct 222(5):2017–2029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, Bennett ML, Münch AE, Chung WS, Peterson TC, Wilton DK, Frouin A, Napier BA, Panicker N, Kumar M, Buckwalter MS, Rowitch DH, Dawson VL, Dawson TM, Stevens B, Barres BA (2017) Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541(7638):481–487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Morel L, Regan M, Higashimori H, Ng SK, Esau C, Vidensky S, Rothstein J, Yang Y (2013) Neuronal exosomal miRNA-dependent translational regulation of astroglial glutamate transporter GLT1. J Biol Chem 288(10):7105–7116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Neo WH, Yap K, Lee SH, Looi LS, Khandelia P, Neo SX, Makeyev EV, Su IH (2014) MicroRNA miR-124 controls the choice between neuronal and astrocyte differentiation by fine-tuning Ezh2 expression. J Biol Chem 289(30):20788–20801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Pogue AI, Cui JG, Li YY, Zhao Y, Culicchia F, Lukiw WJ (2010) Micro RNA-125b (miRNA-125b) function in astrogliosis and glial cell proliferation. Neurosci Lett 476(1):18–22

    Article  CAS  PubMed  Google Scholar 

  52. Bai Y, Zhang Y, Hua J, Yang X, Zhang X, Duan M, Zhu X, Huang W, Chao J, Zhou R, Hu G, Yao H (2016) Silencing microRNA-143 protects the integrity of the blood-brain barrier: implications for methamphetamine abuse. Sci Rep 6:35642

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Wang CY, Yang SH, Tzeng SF (2015) MicroRNA-145 as one negative regulator of astrogliosis. Glia 63(2):194–205

    Article  PubMed  Google Scholar 

  54. Iyer A, Zurolo E, Prabowo A, Fluiter K, Spliet WG, van Rijen PC, Gorter JA, Aronica E (2012) MicroRNA-146a: a key regulator of astrocyte-mediated inflammatory response. PLoS One 7(9):e44789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Ouyang YB, Xu L, Yue S, Liu S, Giffard RG (2014) Neuroprotection by astrocytes in brain ischemia: importance of microRNAs. Neurosci Lett 565:53–58

    Article  CAS  PubMed  Google Scholar 

  56. Hutchison ER, Kawamoto EM, Taub DD, Lal A, Abdelmohsen K, Zhang Y, Wood WH 3rd, Lehrmann E, Camandola S, Becker KG, Gorospe M, Mattson MP (2013) Evidence for miR-181 involvement in neuroinflammatory responses of astrocytes. Glia 61(7):1018–1028

    Article  PubMed  PubMed Central  Google Scholar 

  57. Bhalala OG, Pan L, Sahni V, McGuire TL, Gruner K, Tourtellotte WG, Kessler JA (2012) microRNA-21 regulates astrocytic response following spinal cord injury. J Neurosci 32(50):17935–17947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ziu M, Fletcher L, Rana S, Jimenez DF, Digicaylioglu M (2011) Temporal differences in microRNA expression patterns in astrocytes and neurons after ischemic injury. PLoS One 6(2):e14724

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Jiang Y, Li L, Tan X, Liu B, Zhang Y, Li C (2015) miR-210 mediates vagus nerve stimulation-induced antioxidant stress and anti-apoptosis reactions following cerebral ischemia/reperfusion injury in rats. J Neurochem 134(1):173–181

    Article  CAS  PubMed  Google Scholar 

  60. Shen F, Huang WL, Xing BP, Fang X, Feng M, Jiang CM (2018) Genistein improves the major depression through suppressing the expression of miR-221/222 by targeting connexin 43. Psychiatry Investig 15(10):919–925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Shin JH, Park YM, Kim DH, Moon GJ, Bang OY, Ohn T, Kim HH (2014) Ischemic brain extract increases SDF-1 expression in astrocytes through the CXCR2/miR-223/miR-27b pathway. Biochim Biophys Acta 1839(9):826–836

    Article  CAS  PubMed  Google Scholar 

  62. Li Q, Barres BA (2018) Microglia and macrophages in brain homeostasis and disease. Nat Rev Immunol 18(4):225–242

    Article  CAS  PubMed  Google Scholar 

  63. Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, Mehler MF, Conway SJ, Ng LG, Stanley ER, Samokhvalov IM, Merad M (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330(6005):841–845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Bokobza C, Van Steenwinckel J, Mani S, Mezger V, Fleiss B, Gressens P (2019) Neuroinflammation in preterm babies and autism spectrum disorders. Pediatr Res 85(2):155–165

    Article  PubMed  Google Scholar 

  65. Ponomarev ED, Veremeyko T, Weiner HL (2013) MicroRNAs are universal regulators of differentiation, activation, and polarization of microglia and macrophages in normal and diseased CNS. Glia 61(1):91–103

    Article  PubMed  Google Scholar 

  66. Cho KJ, Song J, Oh Y, Lee JE (2015) MicroRNA-let-7a regulates the function of microglia in inflammation. Mol Cell Neurosci 68:167–176

    Article  CAS  PubMed  Google Scholar 

  67. Zhao H, Wang J, Gao L, Wang R, Liu X, Gao Z, Tao Z, Xu C, Song J, Ji X, Luo Y (2013) MiRNA-424 protects against permanent focal cerebral ischemia injury in mice involving suppressing microglia activation. Stroke 44(6):1706–1713

    Article  CAS  PubMed  Google Scholar 

  68. Li L, Sun Q, Li Y, Yang Y, Yang Y, Chang T, Man M, Zheng L (2015) Overexpression of SIRT1 induced by resveratrol and inhibitor of miR-204 suppresses activation and proliferation of microglia. J Mol Neurosci 56(4):858–867

    Article  CAS  PubMed  Google Scholar 

  69. Yan L, Lee S, Lazzaro DR, Aranda J, Grant MB, Chaqour B (2015) Single and compound knock-outs of MicroRNA (miRNA)-155 and its angiogenic gene target CCN1 in mice alter vascular and neovascular growth in the retina via resident microglia. J Biol Chem 290(38):23264–23281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Mehta A, Baltimore D (2016) MicroRNAs as regulatory elements in immune system logic. Nat Rev Immunol 16(5):279–294

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. School of Biotechnology, National Institute of Technology Calicut, Calicut, India

    Rajanikant G. K. & Gokul Surendran

  2. NeuroDiderot, Inserm, Université de Paris, Paris, France

    Pierre Gressens & Cindy Bokobza

  3. Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition INSERM 1172, Lille, France

    Sreekala S. Nampoothiri

Authors
  1. Rajanikant G. K.
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  2. Pierre Gressens
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  3. Sreekala S. Nampoothiri
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  4. Gokul Surendran
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  5. Cindy Bokobza
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Correspondence to Rajanikant G. K. .

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G. K., R., Gressens, P., Nampoothiri, S.S., Surendran, G., Bokobza, C. (2020). microRNAs in Normal Brain Physiology. In: IschemiRs: MicroRNAs in Ischemic Stroke. Springer, Singapore. https://doi.org/10.1007/978-981-15-4798-0_1

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