Abstract：
:The efficiency of remyelination decreases with age, but the molecular mechanisms responsible for this decline remain only partially understood. In this study, we show that remyelination is regulated by age-dependent epigenetic control of gene expression. In demyelinated young brains, new myelin synthesis is preceded by downregulation of oligodendrocyte differentiation inhibitors and neural stem cell markers, and this is associated with recruitment of histone deacetylases (HDACs) to promoter regions. In demyelinated old brains, HDAC recruitment is inefficient, and this allows the accumulation of transcriptional inhibitors and prevents the subsequent surge in myelin gene expression. Defective remyelination can be recapitulated in vivo in mice receiving systemic administration of pharmacological HDAC inhibitors during cuprizone treatment and is consistent with in vitro results showing defective differentiation of oligodendrocyte progenitors after silencing specific HDAC isoforms. Thus, we suggest that inefficient epigenetic modulation of the oligodendrocyte differentiation program contributes to the age-dependent decline in remyelination efficiency.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Shen S,Sandoval J,Swiss VA,Li J,Dupree J,Franklin RJ,Casaccia-Bonnefil Pdoi
10.1038/nn.2172subject
Has Abstractpub_date
2008-09-01 00:00:00pages
1024-34issue
9eissn
1097-6256issn
1546-1726pii
nn.2172journal_volume
11pub_type
杂志文章abstract：:Neurons in thalamorecipient layers of sensory cortices integrate thalamocortical and intracortical inputs. Although we know that their functional properties can arise from the convergence of thalamic inputs, intracortical circuits could also be involved in thalamocortical transformations of sensory information. We sil...
journal_title：Nature neuroscience
pub_type： 杂志文章
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pub_type： 杂志文章,评审
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pub_type： 杂志文章,评审
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更新日期：2005-11-01 00:00:00
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pub_type： 已发布勘误
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更新日期：2006-01-01 00:00:00
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pub_type： 杂志文章
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更新日期：2014-08-01 00:00:00
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更新日期：2010-06-01 00:00:00
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pub_type： 杂志文章
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更新日期：2005-10-01 00:00:00
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journal_title：Nature neuroscience
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pub_type： 杂志文章
doi：10.1038/nn1403
更新日期：2005-03-01 00:00:00
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pub_type： 杂志文章
doi：10.1038/14801
更新日期：1999-11-01 00:00:00
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journal_title：Nature neuroscience
pub_type： 杂志文章
doi：10.1038/nn1826
更新日期：2007-02-01 00:00:00
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journal_title：Nature neuroscience
pub_type： 杂志文章,评审
doi：10.1038/nn935
更新日期：2002-11-01 00:00:00
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更新日期：2002-04-01 00:00:00
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更新日期：2016-10-01 00:00:00
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更新日期：2014-09-01 00:00:00
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更新日期：2018-11-01 00:00:00
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pub_type： 杂志文章
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更新日期：2005-04-01 00:00:00
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更新日期：2005-12-01 00:00:00
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更新日期：2020-12-21 00:00:00
