BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Age-related epigenetic regulation in the brain and its role in neuronal diseases

  • Kim-Ha, Jeongsil (Department of Integrative Bioscience and Biotechnology, College of Life Sciences, Sejong University) ;
  • Kim, Young-Joon (Department of Integrated Omics for Biomedical Science, Graduate School, Yonsei University)
  • Received : 2016.10.27
  • Accepted : 2016.11.15
  • Published : 2016.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Accumulating evidence indicates many brain functions are mediated by epigenetic regulation of neural genes, and their dysregulations result in neuronal disorders. Experiences such as learning and recall, as well as physical exercise, induce neuronal activation through epigenetic modifications and by changing the noncoding RNA profiles. Animal models, brain samples from patients, and the development of diverse analytical methods have broadened our understanding of epigenetic regulation in the brain. Diverse and specific epigenetic changes are suggested to correlate with neuronal development, learning and memory, aging and age-related neuronal diseases. Although the results show some discrepancies, a careful comparison of the data (including methods, regions and conditions examined) would clarify the problems confronted in understanding epigenetic regulation in the brain.

Keywords

References

  1. Choudhuri S (2011) From Waddington's epigenetic land-scape to small noncoding RNA: some important milestones in the history of epigenetics research. Toxicol Mech Methods 21, 252-274 https://doi.org/10.3109/15376516.2011.559695
  2. Lee SM, Kim-Ha J, Choi WY et al (2016) Interplay of genetic and epigenetic alterations in hepatocellular carcinoma. Epigenomics 8, 993-1005 https://doi.org/10.2217/epi-2016-0027
  3. Fischer A (2014) Epigenetic memory: the Lamarckian brain. EMBO J 33, 945-967 https://doi.org/10.1002/embj.201387637
  4. Pedreira ME, Dimant B and Maldonado H (1996) Inhibitors of protein and RNA synthesis block context memory and long-term habituation in the crab Chas-magnathus. Pharmacol Biochem Behav 54, 611-617 https://doi.org/10.1016/0091-3057(95)02206-6
  5. Arguello AA, Ye X, Bozdagi O et al (2013) CCAAT enhancer binding protein ${\delta}$ plays an essential role in memory consolidation and reconsolidation. J Neurosci 33, 3646-3658 https://doi.org/10.1523/JNEUROSCI.1635-12.2013
  6. Alberini CM and Kandel ER (2014) The regulation of transcription in memory consolidation. Cold Spring Harb Perspect Biol 7, a021741
  7. Feng J, Fouse S and Fan G (2007) Epigenetic regulation of neural gene expression and neuronal function. Pediatr Res 61, 58R-63R https://doi.org/10.1203/pdr.0b013e3180457635
  8. Graff J and Tsai LH (2013) The potential of HDAC inhibitors as cognitive enhancers. Annu Rev Pharmacol Toxicol 53, 311-330 https://doi.org/10.1146/annurev-pharmtox-011112-140216
  9. Fischer A, Sananbenesi F, Wang XY, Dobbin M and Tsai LH (2007) Recovery of learning and memory is associated with chromatin remodelling. Nature 447, 178-182 https://doi.org/10.1038/nature05772
  10. Graff J, Kim D, Dobbin MM and Tsai LH (2011) Epigenetic regulation of gene expression in physiological and pathological brain processes. Physiol Rev 91, 603-649 https://doi.org/10.1152/physrev.00012.2010
  11. Kempermann G, Song H and Gage FH (2015) Neuro-genesis in the Adult Hippocampus. Cold Spring Harb Perspect Biol 7, a018812 https://doi.org/10.1101/cshperspect.a018812
  12. Feng J, Zhou Y, Campbell SL et al (2010) Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons. Nat Neurosci 13, 423-430 https://doi.org/10.1038/nn.2514
  13. Ma DK, Jang MH, Guo JU et al (2009) Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science 323, 1074-1077 https://doi.org/10.1126/science.1166859
  14. Guo JU, Ma DK, Mo H et al (2011) Neuronal activity modifies the DNA methylation landscape in the adult brain. Nat Neurosci 14, 1345-1351 https://doi.org/10.1038/nn.2900
  15. Tan M, Luo H, Lee S et al (2011) Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell 146, 1016-1028 https://doi.org/10.1016/j.cell.2011.08.008
  16. Chwang WB, Arthur JS, Schumacher A and Sweatt JD (2007) The nuclear kinase mitogen-and stress-activated protein kinase 1 regulates hippocampal chromatin remodeling in memory formation. J Neurosci 27, 12732-12742 https://doi.org/10.1523/JNEUROSCI.2522-07.2007
  17. Maharana C, Sharma KP and Sharma SK (2010) Depolarization induces acetylation of histone H2B in the hippocampus. Neuroscience 167, 354-360 https://doi.org/10.1016/j.neuroscience.2010.02.023
  18. Nott A, Watson PM, Robinson JD, Crepaldi L and Riccio A (2008) S-Nitrosylation of histone deacetylase 2 induces chromatin remodelling in neurons. Nature 455, 411-415 https://doi.org/10.1038/nature07238
  19. Tweedie-Cullen RY, Brunner AM, Grossmann J et al (2012) Identification of combinatorial patterns of post-translational modifications on individual histones in the mouse brain. PLoS One 7, e36980 https://doi.org/10.1371/journal.pone.0036980
  20. Graff J and Tsai LH (2013) Histone acetylation: molecular mnemonics on the chromatin. Nat Rev Neurosci 14, 97-111 https://doi.org/10.1038/nrn3427
  21. Adlakha YK and Saini N (2014) Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128. Mol Cancer 13, doi: 10.1186/1476-4598-13-33
  22. Hsieh J and Zhao X (2016) Genetics and Epigenetics in Adult Neurogenesis. Cold Spring Harb Perspect Biol 8, pii: a018911 https://doi.org/10.1101/cshperspect.a018911
  23. Cheng LC, Pastrana E, Tavazoie M and Doetsch F (2009) miR-124 regulates adult neurogenesis in the subventri-cular zone stem cell niche. Nat Neurosci 12, 399-408 https://doi.org/10.1038/nn.2294
  24. Santos MC, Tegge AN, Correa BR et al (2016) miR-124, -128, and -137 Orchestrate Neural Differentiation by Acting on Overlapping Gene Sets Containing a Highly Connected Transcription Factor Network. Stem Cells 34, 220-232 https://doi.org/10.1002/stem.2204
  25. Kim SN, Rhee JH, Song YH et al (2005) Age-dependent changes of gene expression in the Drosophila head. Neurobiol Aging 26, 1083-1091 https://doi.org/10.1016/j.neurobiolaging.2004.06.017
  26. Berchtold NC, Sabbagh MN, Beach TG, Kim RC, Cribbs DH and Cotman CW (2014) Brain gene expression patterns differentiate mild cognitive impairment from normal aged and Alzheimer's disease. Neurobiol Aging 35, 1961-1972 https://doi.org/10.1016/j.neurobiolaging.2014.03.031
  27. Talens RP, Christensen K, Putter H et al (2012) Epigenetic variation during the adult lifespan: cross-sectional and longitudinal data on monozygotic twin pairs. Aging Cell 11, 694-703 https://doi.org/10.1111/j.1474-9726.2012.00835.x
  28. Oh G, Ebrahimi S, Wang SC et al (2016) Epigenetic assimilation in the aging human brain. Genome Biol 17, 76 https://doi.org/10.1186/s13059-016-0946-8
  29. Bollati V, Schwartz J, Wright R et al (2009) Decline in genomic DNA methylation through aging in a cohort of elderly subjects. Mech Ageing Dev 130, 234-239 https://doi.org/10.1016/j.mad.2008.12.003
  30. Chouliaras L, van den Hove DL, Kenis G et al (2012) Age-related increase in levels of 5-hydroxymethylcytosine in mouse hippocampus is prevented by caloric restriction. Curr Alzheimer Res 9, 536-544 https://doi.org/10.2174/156720512800618035
  31. Maegawa S, Hinkal G, Kim HS et al (2010) Widespread and tissue specific age-related DNA methylation changes in mice. Genome Res 20, 332-340 https://doi.org/10.1101/gr.096826.109
  32. Peters MJ, Joehanes R, Pilling LC et al (2015) The transcriptional landscape of age in human peripheral blood. Nat Commun 6, 8570 https://doi.org/10.1038/ncomms9570
  33. Peleg S, Sananbenesi F, Zovoilis A et al (2010) Altered histone acetylation is associated with age-dependent memory impairment in mice. Science 328, 753-756 https://doi.org/10.1126/science.1186088
  34. Chouliaras L, van den Hove DL, Kenis G et al (2013) Histone deacetylase 2 in the mouse hippocampus: attenuation of age-related increase by caloric restriction. Curr Alzheimer Res 10, 868-876 https://doi.org/10.2174/1567205011310080009
  35. Persengiev S, Kondova I, Otting N, Koeppen AH and Bontrop RE (2011) Genome-wide analysis of miRNA expression reveals a potential role for miR-144 in brain aging and spinocerebellar ataxia pathogenesis. Neurobiol Aging 32, 2316.e17-27 https://doi.org/10.1016/j.neurobiolaging.2010.03.014
  36. Inukai S, de Lencastre A, Turner M and Slack F (2012) Novel microRNAs differentially expressed during aging in the mouse brain. PLoS One 7, e40028 https://doi.org/10.1371/journal.pone.0040028
  37. Noren Hooten N, Abdelmohsen K, Gorospe M, Ejiogu N, Zonderman AB and Evans MK (2010) microRNA expression patterns reveal differential expression of target genes with age. PLoS One 5, e10724 https://doi.org/10.1371/journal.pone.0010724
  38. Yin L, Sun Y, Wu J et al (2015) Discovering novel microRNAs and age-related nonlinear changes in rat brains using deep sequencing. Neurobiol Aging 36, 1037-1044 https://doi.org/10.1016/j.neurobiolaging.2014.11.001
  39. Kim J, Yoon H, Chung DE, Brown JL, Belmonte KC and Kim J (2016) miR-186 is decreased in aged brain and suppresses BACE1 expression. J Neurochem 137, 436-445 https://doi.org/10.1111/jnc.13507
  40. Chouliaras L, Mastroeni D, Delvaux E et al (2013) Consistent decrease in global DNA methylation and hydroxymethylation in the hippocampus of Alzheimer's disease patients. Neurobiol Aging 34, 2091-2099 https://doi.org/10.1016/j.neurobiolaging.2013.02.021
  41. Morrison LD, Smith DD and Kish SJ (1996) Brain S-adenosylmethionine levels are severely decreased in Alzheimer's disease. J Neurochem 67, 1328-1331
  42. Coppieters N, Dieriks BV, Lill C, Faull RL, Curtis MA and Dragunow M (2014) Global changes in DNA methylation and hydroxymethylation in Alzheimer's disease human brain. Neurobiol Aging 35, 1334-1344 https://doi.org/10.1016/j.neurobiolaging.2013.11.031
  43. Sanchez-Mut JV and Graff J (2015) Epigenetic Alterations in Alzheimer's Disease. Front Behav Neurosci 9, 347
  44. West RL, Lee JM and Maroun LE (1995) Hypomethylation of the amyloid precursor protein gene in the brain of an Alzheimer's disease patient. J Mol Neurosci 6, 141-146 https://doi.org/10.1007/BF02736773
  45. Barrachina M and Ferrer I (2009) DNA methylation of Alzheimer disease and tauopathy-related genes in postmortem brain. J Neuropathol Exp Neurol 68, 880-891 https://doi.org/10.1097/NEN.0b013e3181af2e46
  46. Wang SC, Oelze B and Schumacher A (2008) Age-specific epigenetic drift in late-onset Alzheimer's disease. PLoS One 3, e2698 https://doi.org/10.1371/journal.pone.0002698
  47. De Jager PL, Srivastava G, Lunnon K et al (2014) Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci. Nat Neurosci 17, 1156-1163 https://doi.org/10.1038/nn.3786
  48. Lunnon K, Smith R, Hannon E et al (2014) Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease. Nat Neurosci 17, 1164-1170 https://doi.org/10.1038/nn.3782
  49. Ricobaraza A, Cuadrado-Tejedor M, Perez-Mediavilla A, Frechilla D, Del Rio J and Garcia-Osta A (2009) Phenylbutyrate ameliorates cognitive deficit and reduces tau pathology in an Alzheimer's disease mouse model. Neuropsychopharmacology 34, 1721-1732 https://doi.org/10.1038/npp.2008.229
  50. Graff J, Rei D, Guan JS et al (2012) An epigenetic blockade of cognitive functions in the neurodegenerating brain. Nature 483, 222-226 https://doi.org/10.1038/nature10849
  51. Marques SC, Lemos R, Ferreiro E et al (2012) Epigenetic regulation of BACE1 in Alzheimer's disease patients and in transgenic mice. Neuroscience 220, 256-266 https://doi.org/10.1016/j.neuroscience.2012.06.029
  52. Lithner CU, Lacor PN, Zhao WQ et al (2013) Disruption of neocortical histone H3 homeostasis by soluble $A{\beta}$: implications for Alzheimer's disease. Neurobiol Aging 34, 2081-2090 https://doi.org/10.1016/j.neurobiolaging.2012.12.028
  53. Ogawa O, Zhu X, Lee HG et al (2003) Ectopic localization of phosphorylated histone H3 in Alzheimer's disease: a mitotic catastrophe? Acta Neuropathol 105, 524-528
  54. Geekiyanage H, Jicha GA, Nelson PT and Chan C (2012) Blood serum miRNA: non-invasive biomarkers for Alzheimer's disease. Exp Neurol 235, 491-496 https://doi.org/10.1016/j.expneurol.2011.11.026
  55. Galimberti D, Villa C, Fenoglio C et al (2014) Circulating miRNAs as potential biomarkers in Alzheimer's disease. J Alzheimers Dis 42, 1261-1267 https://doi.org/10.3233/JAD-140756
  56. Kumar S and Reddy PH (2016) Are circulating microRNAs peripheral biomarkers for Alzheimer's disease? Biochim Biophys Acta 1862, 1617-1627 https://doi.org/10.1016/j.bbadis.2016.06.001
  57. Modi PK, Jaiswal S and Sharma P (2015) Regulation of Neuronal Cell Cycle and Apoptosis by MicroRNA 34a. Mol Cell Biol 36, 84-94
  58. Satake W, Nakabayashi Y, Mizuta I, Hirota Y, Ito C and Kubo M (2009) Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease. Nat Genet 41, 1303-1307 https://doi.org/10.1038/ng.485
  59. Xu W, Tan L and Yu JT (2015) Link between the SNCA gene and parkinsonism. Neurobiol Aging 36, 1505-1518 https://doi.org/10.1016/j.neurobiolaging.2014.10.042
  60. Ai SX, Xu Q, Hu YC et al (2014) Hypomethylation of SNCA in blood of patients with sporadic Parkinson's disease. J Neurol Sci 337, 123-128 https://doi.org/10.1016/j.jns.2013.11.033
  61. Tan YY, Wu L, Zhao ZB et al (2014) Methylation of ${\alpha}$-synuclein and leucine-rich repeat kinase 2 in leukocyte DNA of Parkinson's disease patients. Parkinsonism Relat Disord 20, 308-313 https://doi.org/10.1016/j.parkreldis.2013.12.002
  62. Desplats P, Spencer B, Coffee E et al (2011) Alpha-synuclein sequesters Dnmt1 from the nucleus: a novel mechanism for epigenetic alterations in Lewy body diseases. J Biol Chem 286, 9031-9037 https://doi.org/10.1074/jbc.C110.212589
  63. Coupland KG, Mellick GD, Silburn PA et al (2014) DNA methylation of the MAPT gene in Parkinson's disease cohorts and modulation by vitamin E in vitro. Mov Disord 29, 1606-1614 https://doi.org/10.1002/mds.25784
  64. Goers J, Manning-Bog AB, McCormack AL et al (2003) Nuclear localization of alpha-synuclein and its interaction with histones. Biochemistry 42, 8465-8471 https://doi.org/10.1021/bi0341152
  65. Kontopoulos E, Parvin JD and Feany MB (2006) Alpha-synuclein acts in the nucleus to inhibit histone acetylation and promote neurotoxicity. Hum Mol Genet 15, 3012-3023 https://doi.org/10.1093/hmg/ddl243
  66. Song C, Kanthasamy A, Anantharam V, Sun F and Kanthasamy AG (2010) Environmental neurotoxic pesticide increases histone acetylation to promote apoptosis in dopaminergic neuronal cells: relevance to epigenetic mechanisms of neurodegeneration. Mol Pharmacol 77, 621-632 https://doi.org/10.1124/mol.109.062174
  67. Doxakis E (2010) Post-transcriptional regulation of alpha-synuclein expression by mir-7 and mir-153. J Biol Chem 285, 12726-12734 https://doi.org/10.1074/jbc.M109.086827
  68. Junn E, Lee KW, Jeong BS, Chan TW, Im JY and Mouradian MM (2009) Repression of alpha-synuclein expression and toxicity by microRNA-7. Proc Natl Acad Sci U S A 106, 13052-13057 https://doi.org/10.1073/pnas.0906277106
  69. Kanagaraj N, Beiping H, Dheen ST and Tay SS (2014) Downregulation of miR-124 in MPTP-treated mouse model of Parkinson's disease and MPP iodide-treated MN9D cells modulates the expression of the calpain/cdk5 pathway proteins. Neuroscience 272, 167-179 https://doi.org/10.1016/j.neuroscience.2014.04.039
  70. Kim J, Inoue K, Ishii J et al (2007) A MicroRNA feedback circuit in midbrain dopamine neurons. Science 317, 1220-1224 https://doi.org/10.1126/science.1140481
  71. Lungu G, Stoica G and Ambrus A (2013) MicroRNA profiling and the role of microRNA-132 in neuro-degeneration using a rat model. Neurosci Lett 553, 153-158 https://doi.org/10.1016/j.neulet.2013.08.001
  72. Margis R, Margis R and Rieder CRM (2011) Identification of blood microRNAs associated to Parkinson's disease. J Biotechnol 152, 96-101 https://doi.org/10.1016/j.jbiotec.2011.01.023
  73. Cardo LF, Coto E, de Mena L et al (2013) Profile of microRNAs in the plasma of Parkinson's disease patients and healthy controls. J Neurol 260, 1420-1422 https://doi.org/10.1007/s00415-013-6900-8
  74. Hoss AG, Labadorf A, Beach TG, Latourelle JC and Myers RH (2016) microRNA Profiles in Parkinson's Disease Prefrontal Cortex. Front Aging Neurosci 8, 36
  75. Nucifora FC Jr, Sasaki M, Peters MF et al (2001) Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity. Science 291, 2423-2428 https://doi.org/10.1126/science.1056784
  76. Steffan JS, Bodai L, Pallos J et al (2001) Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature 413, 739-743 https://doi.org/10.1038/35099568
  77. Sadri-Vakili G, Bouzou B, Benn CL et al (2007) Histones associated with downregulated genes are hypo-acetylated in Huntington's disease models. Hum Mol Genet 16, 1293-1306 https://doi.org/10.1093/hmg/ddm078
  78. Hu Y, Chopra V, Chopra R et al (2011) Transcriptional modulator H2A histone family, member Y (H2AFY) marks Huntington disease activity in man and mouse. Proc Natl Acad Sci U S A 108, 17141-17146 https://doi.org/10.1073/pnas.1104409108
  79. Ryu H, Lee J, Hagerty SW et al (2006) ESET/SETDB1 gene expression and histone H3 (K9) trime-thylation in Huntington's disease. Proc Natl Acad Sci U S A 103, 19176-19181 https://doi.org/10.1073/pnas.0606373103
  80. Ng CW, Yildirim F, Yap YS et al (2013) Extensive changes in DNA methylation are associated with expression of mutant huntingtin. Proc Natl Acad Sci U S A 110, 2354-2359 https://doi.org/10.1073/pnas.1221292110
  81. De Souza RA, Islam SA, McEwen LM et al (2016) DNA methylation profiling in human Huntington's disease brain. Hum Mol Genet 25, 2013-2030 https://doi.org/10.1093/hmg/ddw076
  82. Diez-Planelles C, Sanchez-Lozano P, Crespo MC et al (2016) Circulating microRNAs in Huntington's disease: Emerging mediators in metabolic impairment. Pharmacol Res 108, 102-110 https://doi.org/10.1016/j.phrs.2016.05.005
  83. Conaco C, Otto S, Han JJ and Mandel G (2006) Reciprocal actions of REST and microRNA promote neuronal identity. Proc Natl Acad Sci U S A 103, 2422-2427 https://doi.org/10.1073/pnas.0511041103
  84. Soldati C, Bithell A, Johnston C, Wong KY, Stanton LW and Buckley NJ (2013) Dysregulation of REST-regulated coding and non-coding RNAs in a cellular model of Huntington's disease. J Neurochem 124, 418-430 https://doi.org/10.1111/jnc.12090
  85. Savas JN, Makusky A, Ottosen S et al (2008) Huntington's disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P bodies. Proc Natl Acad Sci U S A 105, 10820-10825 https://doi.org/10.1073/pnas.0800658105
  86. Machida T, Tomofuji T, Ekuni D et al (2015) MicroRNAs in Salivary Exosome as Potential Biomarkers of Aging. Int J Mol Sci 16, 21294-21309 https://doi.org/10.3390/ijms160921294
  87. Jung HJ and Suh Y (2014) Circulating miRNAs in ageing and ageing-related diseases. J Genet Genomics 41, 465-472 https://doi.org/10.1016/j.jgg.2014.07.003

Cited by

  1. Dementia: beyond multi-morbidity vol.16, pp.4, 2017, https://doi.org/10.1108/JPMH-05-2017-0019
  2. Genomics: New Light on Alzheimer’s Disease Research vol.19, pp.12, 2018, https://doi.org/10.3390/ijms19123771
  3. Can Long-Term Regular Practice of Physical Exercises Including Taichi Improve Finger Tapping of Patients Presenting With Mild Cognitive Impairment? vol.9, pp.1664-042X, 2018, https://doi.org/10.3389/fphys.2018.01396