Epigenetic Mechanisms Regulating Memory Formation in Health and Disease

Chapter
Part of the Research and Perspectives in Neurosciences book series (NEUROSCIENCE)

Abstract

In 1984, Francis Crick (1916–2004) proposed that “memory might be coded in alterations to particular stretches of chromosomal DNA” (Crick Nature 312:101, 1984). Although the response to this idea was relatively modest at the time, 20 years later it was shown that histone acetylation, a common form of epigenetic modification, was dynamically altered during memory formation (Levenson et al. J Biol Chem 279:40545–40559, 2004). Histone acetylation is regulated by the opposing activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs; Bird Nature 447:396–398, 2007; Berger et al. Genes Dev 23:781–783, 2009). HAT proteins are subdivided into five families that have high sequence similarity and related substrate specificity (Kimura et al. J Biochem 138:647–662, 2005). HDACs belong to an ancient protein family that is found in archea, eubacteria, plants, fungi and animals and that requires a Zn2+ ion as a cofactor. Based on phylogenetic analysis, HDACs are grouped into three classes (Class I, II and IV).

Keywords

Amyotrophic Lateral Sclerosis Histone Acetylation Memory Formation Sodium Butyrate H4K12 Acetylation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Alzheimer’s Disease International (2009) World Alzheimer Report 2009: The global economic impact of dementia. Alzheimer’s Disease International: The International Federation of Alzheimer’s Disease and Related Disorders Societies, Inc, LondonGoogle Scholar
  2. Alzheimer’s Disease International (2010) World Alzheimer Report 2010: The global economic impact of dementia. Alzheimer’s Disease International: The International Federation of Alzheimer’s Disease and Related Disorders Societies, Inc, LondonGoogle Scholar
  3. Augustinack JC, Sanders JL, Tsai LH, Hyman BT (2002) Colocalization and fluorescence resonance energy transfer between cdk5 and AT8 suggests a close association in pre-neurofibrillary tangles and neurofibrillary tangles. J Neuropathol Exp Neurol 61:557–564PubMedGoogle Scholar
  4. Baumann K (1993) Abnormal Alzheimer-like phosphorylation of tau-protein by cyclin-dependent kinases cdk2 and cdk5. FEBS Lett 336:417–424PubMedCrossRefGoogle Scholar
  5. Chae T, Kwon YT, Bronson R, Dikkes P, En L, Tsai LH (1997) Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality. Neuron 18:29–42PubMedCrossRefGoogle Scholar
  6. Chuang DM, Leng Y, Marinova Z, Kim HJ, Chiu CT (2009) Multiple roles of HDAC inhibition in neurodegenerative conditions. Trends Neurosci 32:591–601PubMedCrossRefGoogle Scholar
  7. Chwang WB, O'Riordan KJ, Levenson JM, Sweatt JD (2006) ERK/MAPK regulates hippocampal histone phosphorylation following contextual fear conditioning. Learn Mem 13:322–328PubMedCrossRefGoogle Scholar
  8. Cruz JC, Tseng H-C, Goldman JA, Shih H, Tsai L-H (2003) Aberrant Cdk5 activation by p25 triggers pathological events leading to neurodegeneration and neurofibrillary tangles. Neuron 40:471–483PubMedCrossRefGoogle Scholar
  9. de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB (2003) Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 370:737–749PubMedCrossRefGoogle Scholar
  10. Fischer A, Sananbenesi F, Pang PT, Lu B, Tsai L-H (2005) Opposing roles of transient and prolonged expression of p25 in synaptic plasticity and hippocampus-dependent memory. Neuron 48:825–838PubMedCrossRefGoogle Scholar
  11. Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai LH (2007) Recovery of learning and memory is associated with chromatin remodelling. Nature 447:178–182PubMedCrossRefGoogle Scholar
  12. Fontan-Lozano A, Romero-Granados R, Troncoso J, Munera A, Delgado-Garcia JM, Carrion AM (2008) Histone deacetylase inhibitors improve learning consolidation in young and in KA-induced-neurodegeneration and SAMP-8-mutant mice. Mol Cell Neurosci 39:193–201PubMedCrossRefGoogle Scholar
  13. Gauthier S, Aisen PS, Ferris SH, Saumier D, Duong A, Haine D, Garceau D, Suhy J, Oh J, Lau W, Sampalis J (2009) Effect of tramiprosate in patients with mild-to-moderate Alzheimer’s disease: exploratory analyses of the MRI sub-group of the Alphase study. J Nutr Health Aging 13:550–557PubMedCrossRefGoogle Scholar
  14. Guan J-S, Haggarty SJ, Giacometti E, Dannenberg J-H, Joseph N, Gao J, Nieland TJF, Zhou Y, Wang X, Mazitschek R, Bradner JE, Depinho RA, Jaenisch R, Tsai L-H (2009) HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 459:55–60PubMedCrossRefGoogle Scholar
  15. Hardy J (2006) A hundred years of Alzheimer’s disease research. Neuron 52:3–13PubMedCrossRefGoogle Scholar
  16. Holmes C, Boche D, Wilkinson D, Yadegarfar G, Hopkins V, Bayer A, Jones RW, Bullock R, Love S, Neal JW, Zotova E, Nicoll JA (2008) Long-term effects of Abeta42 immunisation in Alzheimer’s disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet 372:216–223PubMedCrossRefGoogle Scholar
  17. Kilgore M, Miller CA, Fass DM, Hennig KM, Haggarty SJ, Sweatt JD, Rumbaugh G (2009) Inhibitors of class 1 histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimer’s disease. Neuropsychopharmacology 35:870–880PubMedCrossRefGoogle Scholar
  18. Kitazawa M, Oddo S, Yamasaki TR, Green KN, LaFerla FM (2005) Lipopolysaccharide-induced inflammation exacerbates tau pathology by a cyclin-dependent kinase 5-mediated pathway in a transgenic model of Alzheimer’s disease. J Neurosci 25:8843–8853PubMedCrossRefGoogle Scholar
  19. Ko J, Humbert S, Bronson RT, Takahashi S, Kulkarni AB, Li E, Tsai LH (2001) p35 and p39 are essential for cyclin-dependent kinase 5 function during neurodevelopment. J Neurosci 21:6758–6771PubMedGoogle Scholar
  20. Koshibu K, Graff J, Beullens M, Heitz FD, Berchtold D, Russig H, Farinelli M, Bollen M, Mansuy IM (2009) Protein phosphatase 1 regulates the histone code for long-term memory. J Neurosci 29:13079–13089PubMedCrossRefGoogle Scholar
  21. Kwon YT, Tsai LH (1998) A novel disruption of cortical development in p35(−/−) mice distinct from reeler. J Comp Neurol 395:510–522PubMedCrossRefGoogle Scholar
  22. Lee MS, Kwon YT, Li M, Peng J, Friedlander RM, Tsai LH (2000) Neurotoxicity induces cleavage of p35 to p25 by calpain. Nature 405:360–364PubMedCrossRefGoogle Scholar
  23. Levenson JM, O'Riordan KJ, Brown KD, Trinh MA, Molfese DL, Sweatt JD (2004) Regulation of histone acetylation during memory formation in the hippocampus. J Biol Chem 279:40545–40559PubMedCrossRefGoogle Scholar
  24. Mai A, Rotili D, Valente S, Kazantsev AG (2009) Histone deacetylase inhibitors and neurodegenerative disorders: holding the promise. Curr Pharm Des 15:3940–3957PubMedCrossRefGoogle Scholar
  25. Muyllaert D, Terwel D, Kremer A, Sennvik K, Borghgraef P, Devijver H, Dewachter I, Van Leuven F (2008) Neurodegeneration and neuroinflammation in cdk5/p25-inducible mice: a model for hippocampal sclerosis and neocortical degeneration. Am J Pathol 172:470–485PubMedCrossRefGoogle Scholar
  26. Nguyen MD, Lariviere RC, Julien JP (2001) Deregulation of Cdk5 in a mouse model of ALS: toxicity alleviated by perikaryal neurofilament inclusions. Neuron 30:135–147PubMedCrossRefGoogle Scholar
  27. Nikolic M, Dudek H, Kwon YT, Ramos YFM, Tsai LH (1996) The cdk5/p35 kinase is essential for neurite outgrowth during neuronal differentiation. Genes Dev 10:816–825PubMedCrossRefGoogle Scholar
  28. Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J, Guillozet-Bongaarts A, Ohno M, Disterhoft J, Van Eldik L, Berry R, Vassar R (2006) Intraneuronal β-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer’s disease mutations: potential factors in amyloid plaque formation. J Neurosci 26:10129–10140PubMedCrossRefGoogle Scholar
  29. Otth C, Concha II, Arendt T, Stieler J, Schliebs R, Gonzalez-Billault C, Maccioni RB (2002) AbetaPP induces cdk5-dependent tau hyperphosphorylation in transgenic mice Tg2576. J Alzheimers Dis 4:417–430PubMedGoogle Scholar
  30. Paoletti P, Vila I, Rife M, Lizcano JM, Alberch J, Gines S (2008) Dopaminergic and glutamatergic signaling crosstalk in Huntington’s disease neurodegeneration: the role of p25/cyclin-dependent kinase 5. J Neurosci 28:10090–10101PubMedCrossRefGoogle Scholar
  31. Patrick GN, Zukerberg L, Nikolic M, de la Monte S, Dikkes P, Tsai LH (1999) Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration. Nature 402:615–622PubMedCrossRefGoogle Scholar
  32. Patton RL, Kalback WM, Esh CL, Kokjohn TA, Van Vickle GD, Luehrs DC, Kuo YM, Lopez J, Brune D, Ferrer I, Masliah E, Newel AJ, Beach TG, Castano EM, Roher AE (2006) Amyloid-beta peptide remnants in AN-1792-immunized Alzheimer’s disease patients: a biochemical analysis. Am J Pathol 169:1048–1063PubMedCrossRefGoogle Scholar
  33. Paudel HK, Lew J, Ali Z, Wang JH (1993) Brain proline-directed protein kinase phosphorylates tau on sites that are abnormally phosphorylated in tau associated with Alzheimer’s paired helical filaments. J Biol Chem 268:23512–23518PubMedGoogle Scholar
  34. Pei JJ, Grundke-Iqbal I, Iqbal K, Bogdanovic N, Winblad B, Cowburn RF (1998) Accumulation of cyclin-dependent kinase 5 (cdk5) in neurons with early stages of Alzheimer’s disease neurofibrillary degeneration. Brain Res 797:267–277PubMedCrossRefGoogle Scholar
  35. Peleg S, Sananbenesi F, Zovoilis A, Burkhardt S, Bahari-Javan S, Agis-Balboa RC, Cota P, Wittnam JL, Gogol-Doering A, Opitz L, Salinas-Riester G, Dettenhofer M, Kang H, Farinelli L, Chen W, Fischer A (2010) Altered histone acetylation is associated with age-dependent memory impairment in mice. Science 328:753–756PubMedCrossRefGoogle Scholar
  36. Ricobaraza A, Cuadrado-Tejedor M, Perez-Mediavilla A, Frechilla D, Del Rio J, Garcia-Osta A (2009) Phenylbutyrate ameliorates cognitive deficit and reduces tau pathology in an Alzheimer’s disease mouse model. Neuropsychopharmacology 34:1721–1732PubMedCrossRefGoogle Scholar
  37. Saumier D, Duong A, Haine D, Garceau D, Sampalis J (2009) Domain-specific cognitive effects of tramiprosate in patients with mild to moderate Alzheimer’s disease: ADAS-cog subscale results from the Alphase study. J Nutr Health Aging 13:808–812PubMedCrossRefGoogle Scholar
  38. Saura CA, Choi S-Y, Beglopoulos V, Malkani S, Zhang D, Rao BSS, Chattarji S, Kelleher Iii RJ, Kandel ER, Duff K, Kirkwood A, Shen J (2004) Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Neuron 42:23–36PubMedCrossRefGoogle Scholar
  39. Selvi BR, Cassel J-C, Kundu TK, Boutillier A-L (2010) Tuning acetylation levels with HAT activators: therapeutic strategy in neurodegenerative diseases. Biochim BiophysActa (BBA) 1799:840–853CrossRefGoogle Scholar
  40. Sen A, Thom M, Martinian L, Jacobs T, Nikolic M, Sisodiya SM (2006) Deregulation of cdk5 in hippocampal sclerosis. J Neuropathol Exp Neurol 65:55–66PubMedCrossRefGoogle Scholar
  41. Smith PD, Crocker SJ, Jackson-Lewis V, Jordan-Sciutto KL, Hayley S, Mount MP, O'Hare MJ, Callaghan S, Slack RS, Przedborski S, Anisman H, Park DS (2003) Cyclin-dependent kinase 5 is a mediator of dopaminergic neuron loss in a mouse model of Parkinson’s disease. Proc Natl Acad Sci U S A 100:13650–13655PubMedCrossRefGoogle Scholar
  42. Talan J (2009) High-dose Bapineuzumab puts some AD patients at risk for vasogenic cerebral edema: those taking largest dose removed from trials. Neurol Today 9:4Google Scholar
  43. Tang D, Yeung J, Lee KY, Matsushita M, Matsui H, Tomizawa K, Hatase O, Wang JH (1995) An isoform of the neuronal cyclin-dependent kinase 5 (Cdk5) activator. J Biol Chem 270:26897–26903PubMedCrossRefGoogle Scholar
  44. Tsai L-H, Delalle I, Caviness VS, Chae T, Harlow E (1994) p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5. Nature 371:419–423PubMedCrossRefGoogle Scholar
  45. Tseng HC, Zhou Y, Shen Y, Tsai LH (2002) A survey of Cdk5 activator p35 and p25 levels in Alzheimer’s disease brains. FEBS Lett 523:58–62PubMedCrossRefGoogle Scholar
  46. Vecsey CG, Hawk JD, Lattal KM, Stein JM, Fabian SA, Attner MA, Cabrera SM, McDonough CB, Brindle PK, Abel T, Wood MA (2007) Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB:CBP-dependent transcriptional activation. J Neurosci 27:6128–6140PubMedCrossRefGoogle Scholar
  47. Wenzel HJ, Tamse CT, Schwartzkroin PA (2007) Dentate development in organotypic hippocampal slice cultures from p35 knockout mice. Dev Neurosci 29:99–112PubMedCrossRefGoogle Scholar
  48. Zhang Z, Simpkins JW (2010a) An okadaic acid-induced model of tauopathy and cognitive deficiency. Brain Res 1359:233–246PubMedCrossRefGoogle Scholar
  49. Zhang Z, Simpkins JW (2010b) Okadaic acid induces tau phosphorylation in SH-SY5Y cells in an estrogen-preventable manner. Brain Res 1345:176–181PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Department of Brain and Cognitive Sciences, Picower Institute for Learning and MemoryMassachusetts Institute of TechnologyCambridgeUSA
  2. 2.Howard Hughes Medical InstituteCambridgeUSA
  3. 3.The Stanley Center for Psychiatric ResearchBroad Institute for Harvard and MITCambridgeUSA

Personalised recommendations