title: Altered histone acetylation is associated with age-dependent memory impairment in mice.
abstract: As the human life span increases, the number of people suffering from cognitive decline is rising dramatically. The mechanisms underlying age-associated memory impairment are, however, not understood. Here we show that memory disturbances in the aging brain of the mouse are associated with altered hippocampal chromatin plasticity. During learning, aged mice display a specific deregulation of histone H4 lysine 12 (H4K12) acetylation and fail to initiate a hippocampal gene expression program associated with memory consolidation. Restoration of physiological H4K12 acetylation reinstates the expression of learning-induced genes and leads to the recovery of cognitive abilities. Our data suggest that deregulated H4K12 acetylation may represent an early biomarker of an impaired genome-environment interaction in the aging mouse brain.
authors.affiliation: Laboratory for Aging and Cognitive Diseases, European Neuroscience Institute, Grisebach Str. 5, D-37077 Goettingen, Germany.
authors.forename: Shahaf
authors.initials: S
authors.lastname: Peleg
authors.forename: Farahnaz
authors.initials: F
authors.lastname: Sananbenesi
authors.forename: Athanasios
authors.initials: A
authors.lastname: Zovoilis
authors.forename: Susanne
authors.initials: S
authors.lastname: Burkhardt
authors.forename: Sanaz
authors.initials: S
authors.lastname: Bahari-Javan
authors.forename: Roberto Carlos
authors.initials: RC
authors.lastname: Agis-Balboa
authors.forename: Perla
authors.initials: P
authors.lastname: Cota
authors.forename: Jessica Lee
authors.initials: JL
authors.lastname: Wittnam
authors.forename: Andreas
authors.initials: A
authors.lastname: Gogol-Doering
authors.forename: Lennart
authors.initials: L
authors.lastname: Opitz
authors.forename: Gabriella
authors.initials: G
authors.lastname: Salinas-Riester
authors.forename: Markus
authors.initials: M
authors.lastname: Dettenhofer
authors.forename: Hui
authors.initials: H
authors.lastname: Kang
authors.forename: Laurent
authors.initials: L
authors.lastname: Farinelli
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: André
authors.initials: A
authors.lastname: Fischer
mesh_terms: D000107:Acetylation; D000375:Aging / Q000235:genetics*; D000818:Animals; D002843:Chromatin / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D003213:Conditioning, Psychological; D044127:Epigenesis, Genetic; D005239:Fear; D000080865:Formins; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000378:metabolism / Q000494:pharmacology; D006657:Histones / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000494:pharmacology; D007858:Learning / Q000187:drug effects; D008239:Lysine / Q000378:metabolism; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D002843:Chromatin; D000080865:Formins; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C549436:formin 2 protein, mouse; C528828:suberoyl bis-hydroxamic acid; D008239:Lysine