schliessen

Filtern

 

Bibliotheken

HDAC2 negatively regulates memory formation and synaptic plasticity

Chromatin modifications, especially histone-tail acetylation, have been implicated in memory formation. Increased histone-tail acetylation induced by inhibitors of histone deacetylases (HDACis) facilitates learning and memory in wild-type mice as well as in mouse models of neurodegeneration. Harness... Full description

Journal Title: Nature 2009, Vol.459(7243), p.55
Main Author: Ji-Song Guan
Other Authors: Stephen J. Haggarty , Emanuela Giacometti , Jan-Hermen Dannenberg , Nadine Joseph , Jun Gao , Thomas J. F. Nieland , Ying Zhou , Xinyu Wang , Ralph Mazitschek , James E. Bradner , Ronald A. Depinho , Rudolf Jaenisch , Li-Huei Tsai
Format: Electronic Article Electronic Article
Language:
Subjects:
ID: ISSN: 0028-0836 ; E-ISSN: 1476-4687 ; DOI: 10.1038/nature07925
Link: http://dx.doi.org/10.1038/nature07925
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: nature_a10.1038/nature07925
title: HDAC2 negatively regulates memory formation and synaptic plasticity
format: Article
creator:
  • Ji-Song Guan
  • Stephen J. Haggarty
  • Emanuela Giacometti
  • Jan-Hermen Dannenberg
  • Nadine Joseph
  • Jun Gao
  • Thomas J. F. Nieland
  • Ying Zhou
  • Xinyu Wang
  • Ralph Mazitschek
  • James E. Bradner
  • Ronald A. Depinho
  • Rudolf Jaenisch
  • Li-Huei Tsai
subjects:
  • Animals–Pharmacology
  • Butyrates–Physiology
  • Dendritic Spines–Physiology
  • Electrical Synapses–Metabolism
  • Female–Deficiency
  • Gene Expression Regulation–Genetics
  • Hippocampus–Metabolism
  • Histone Deacetylase 1–Pharmacology
  • Histone Deacetylase 2–Drug Effects
  • Histone Deacetylase Inhibitors–Drug Effects
  • Histone Deacetylases–Physiology
  • Histone Deacetylases–Metabolism
  • Histone Deacetylases–Genetics
  • Hydroxamic Acids–Antagonists & Inhibitors
  • Learning–Genetics
  • Male–Metabolism
  • Memory–Pharmacology
  • Memory–Pharmacology
  • Mice–Pharmacology
  • Mice, Inbred C57bl–Pharmacology
  • Mice, Knockout–Pharmacology
  • Neurons–Pharmacology
  • Promoter Regions, Genetic–Pharmacology
  • Repressor Proteins–Pharmacology
  • Repressor Proteins–Pharmacology
  • Repressor Proteins–Pharmacology
  • Sodium–Pharmacology
  • Rodents
  • Genetics
  • Proteins
  • Studies
  • Software
  • DNA Damage
  • Changes
  • Memory
  • Butyrates
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Repressor Proteins
  • Vorinostat
  • Sodium
  • Hdac1 Protein, Mouse
  • Hdac2 Protein, Mouse
  • Histone Deacetylase 1
  • Histone Deacetylase 2
  • Histone Deacetylases
ispartof: Nature, 2009, Vol.459(7243), p.55
description: Chromatin modifications, especially histone-tail acetylation, have been implicated in memory formation. Increased histone-tail acetylation induced by inhibitors of histone deacetylases (HDACis) facilitates learning and memory in wild-type mice as well as in mouse models of neurodegeneration. Harnessing the therapeutic potential of HDACis requires knowledge of the specific HDAC family member(s) linked to cognitive enhancement. Here we show that neuron-specific overexpression of HDAC2, but not that of HDAC1, decreased dendritic spine density, synapse number, synaptic plasticity and memory formation. Conversely, Hdac2 deficiency resulted in increased synapse number and memory facilitation, similar to chronic treatment with HDACis in mice. Notably, reduced synapse number and learning impairment of HDAC2-overexpressing mice were ameliorated by chronic treatment with HDACis. Correspondingly, treatment with HDACis failed to further facilitate memory formation in Hdac2-deficient mice. Furthermore, analysis of promoter occupancy revealed an association of HDAC2 with the promoters of genes implicated in synaptic plasticity and memory formation. Taken together, our results suggest that HDAC2 functions in modulating synaptic plasticity and long-lasting changes of neural circuits, which in turn negatively regulates learning and memory. These observations encourage the development and testing of HDAC2-selective inhibitors for human diseases associated with memory impairment. [PUBLICATION ]
language:
source:
identifier: ISSN: 0028-0836 ; E-ISSN: 1476-4687 ; DOI: 10.1038/nature07925
fulltext: fulltext
issn:
  • 0028-0836
  • 00280836
  • 1476-4687
  • 14764687
url: Link


@attributes
ID1764683771
RANK0.06999999
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
LOCALfalse
PrimoNMBib
record
control
sourcerecordid10.1038/nature07925
sourceidnature_a
recordidTN_nature_a10.1038/nature07925
sourcesystemOther
pqid67222430
galeid199991239
display
typearticle
titleHDAC2 negatively regulates memory formation and synaptic plasticity
creatorJi-Song Guan ; Stephen J. Haggarty ; Emanuela Giacometti ; Jan-Hermen Dannenberg ; Nadine Joseph ; Jun Gao ; Thomas J. F. Nieland ; Ying Zhou ; Xinyu Wang ; Ralph Mazitschek ; James E. Bradner ; Ronald A. Depinho ; Rudolf Jaenisch ; Li-Huei Tsai
ispartofNature, 2009, Vol.459(7243), p.55
identifier
source
subjectAnimals–Pharmacology ; Butyrates–Physiology ; Dendritic Spines–Physiology ; Electrical Synapses–Metabolism ; Female–Deficiency ; Gene Expression Regulation–Genetics ; Hippocampus–Metabolism ; Histone Deacetylase 1–Pharmacology ; Histone Deacetylase 2–Drug Effects ; Histone Deacetylase Inhibitors–Drug Effects ; Histone Deacetylases–Physiology ; Histone Deacetylases–Metabolism ; Histone Deacetylases–Genetics ; Hydroxamic Acids–Antagonists & Inhibitors ; Learning–Genetics ; Male–Metabolism ; Memory–Pharmacology ; Memory–Pharmacology ; Mice–Pharmacology ; Mice, Inbred C57bl–Pharmacology ; Mice, Knockout–Pharmacology ; Neurons–Pharmacology ; Promoter Regions, Genetic–Pharmacology ; Repressor Proteins–Pharmacology ; Repressor Proteins–Pharmacology ; Repressor Proteins–Pharmacology ; Sodium–Pharmacology ; Rodents ; Genetics ; Proteins ; Studies ; Software ; DNA Damage ; Changes ; Memory ; Butyrates ; Histone Deacetylase Inhibitors ; Hydroxamic Acids ; Repressor Proteins ; Vorinostat ; Sodium ; Hdac1 Protein, Mouse ; Hdac2 Protein, Mouse ; Histone Deacetylase 1 ; Histone Deacetylase 2 ; Histone Deacetylases;
descriptionChromatin modifications, especially histone-tail acetylation, have been implicated in memory formation. Increased histone-tail acetylation induced by inhibitors of histone deacetylases (HDACis) facilitates learning and memory in wild-type mice as well as in mouse models of neurodegeneration. Harnessing the therapeutic potential of HDACis requires knowledge of the specific HDAC family member(s) linked to cognitive enhancement. Here we show that neuron-specific overexpression of HDAC2, but not that of HDAC1, decreased dendritic spine density, synapse number, synaptic plasticity and memory formation. Conversely, Hdac2 deficiency resulted in increased synapse number and memory facilitation, similar to chronic treatment with HDACis in mice. Notably, reduced synapse number and learning impairment of HDAC2-overexpressing mice were ameliorated by chronic treatment with HDACis. Correspondingly, treatment with HDACis failed to further facilitate memory formation in Hdac2-deficient mice. Furthermore, analysis of promoter occupancy revealed an association of HDAC2 with the promoters of genes implicated in synaptic plasticity and memory formation. Taken together, our results suggest that HDAC2 functions in modulating synaptic plasticity and long-lasting changes of neural circuits, which in turn negatively regulates learning and memory. These observations encourage the development and testing of HDAC2-selective inhibitors for human diseases associated with memory impairment. [PUBLICATION ]
version10
lds50peer_reviewed
links
openurl$$Topenurl_article
backlink$$Uhttp://dx.doi.org/10.1038/nature07925$$EView_this_record_in_Nature
openurlfulltext$$Topenurlfull_article
search
creatorcontrib
0Ji-Song Guan
1Stephen J. Haggarty
2Emanuela Giacometti
3Jan-Hermen Dannenberg
4Nadine Joseph
5Jun Gao
6Thomas J. F. Nieland
7Ying Zhou
8Xinyu Wang
9Ralph Mazitschek
10James E. Bradner
11Ronald A. Depinho
12Rudolf Jaenisch
13Li-Huei Tsai
titleHDAC2 negatively regulates memory formation and synaptic plasticity
general
0Nature Publishing Group
110.1038/nature07925
2nature.com (Nature Publishing Group)
sourceidnature_a
recordidnature_a10.1038/nature07925
issn
00028-0836
100280836
21476-4687
314764687
rsrctypearticle
creationdate2009
searchscopenature_a
scopenature_a
lsr30VSR-Enriched:[pqid, galeid, eissn, subject, description, pages]
sort
titleHDAC2 negatively regulates memory formation and synaptic plasticity
authorJi-Song Guan ; Stephen J. Haggarty ; Emanuela Giacometti ; Jan-Hermen Dannenberg ; Nadine Joseph ; Jun Gao ; Thomas J. F. Nieland ; Ying Zhou ; Xinyu Wang ; Ralph Mazitschek ; James E. Bradner ; Ronald A. Depinho ; Rudolf Jaenisch ; Li-Huei Tsai
creationdate20090507
facets
frbrgroupid5215472660543118176
frbrtype5
creationdate2009
collectionnature.com (Nature Publishing Group)
prefilterarticles
rsrctypearticles
creatorcontrib
0Ji-Song Guan
1Stephen J. Haggarty
2Emanuela Giacometti
3Jan-Hermen Dannenberg
4Nadine Joseph
5Jun Gao
6Thomas J. F. Nieland
7Ying Zhou
8Xinyu Wang
9Ralph Mazitschek
10James E. Bradner
11Ronald A. Depinho
12Rudolf Jaenisch
13Li-Huei Tsai
jtitleNature
toplevelpeer_reviewed
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
au
0Ji-Song Guan
1Stephen J. Haggarty
2Emanuela Giacometti
3Jan-Hermen Dannenberg
4Nadine Joseph
5Jun Gao
6Thomas J. F. Nieland
7Ying Zhou
8Xinyu Wang
9Ralph Mazitschek
10James E. Bradner
11Ronald A. Depinho
12Rudolf Jaenisch
13Li-Huei Tsai
atitleHDAC2 negatively regulates memory formation and synaptic plasticity
jtitleNature
risdate20090507
volume459
issue7243
spage55
issn0028-0836
genrearticle
ristypeJOUR
pubNature Publishing Group
doi10.1038/nature07925
pages55-60
eissn14764687
date2009-05-07