Altered Histone Acetylation Is Associated with Age-Dependent Memory Impairment in Mice

被引：726

作者：

Peleg, Shahaf ^{[1
]}

Sananbenesi, Farahnaz ^{[1
]}

Zovoilis, Athanasios ^{[1
]}

Burkhardt, Susanne ^{[1
]}

Bahari-Javan, Sanaz ^{[1
]}

Agis-Balboa, Roberto Carlos ^{[1
]}

Cota, Perla ^{[1
]}

Wittnam, Jessica Lee ^{[1
]}

Gogol-Doering, Andreas ^{[2
]}

Opitz, Lennart ^{[3
]}

Salinas-Riester, Gabriella ^{[3
]}

Dettenhofer, Markus ^{[4
]}

Kang, Hui ^{[2
]}

Farinelli, Laurent ^{[5
]}

Chen, Wei ^{[2
]}

Fischer, Andre ^{[1
]}

机构：

[1] European Neurosci Inst, Lab Aging & Cognit Dis, D-37077 Gottingen, Germany

[2] Max Delbruck Ctr Mol Med, Inst Med Syst Biol, D-13125 Berlin, Germany

[3] Univ Gottingen, DNA Microarray Facil, D-37073 Gottingen, Germany

[4] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[5] Fasteris SA, CH-1228 Plan Les Ouates, Switzerland

来源：

SCIENCE | 2010年 / 328卷 / 5979期

关键词：

CENTRAL-NERVOUS-SYSTEM; GENE-EXPRESSION; SYNAPTIC PLASTICITY; CHIP-SEQ; BRAIN; FORMIN-2; PROTEIN; LTP;

D O I：

10.1126/science.1186088

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：753 / 756

页数：4

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