HDAC activity is required for BDNF to increase quantal neurotransmitter release and dendritic spine density in CA1 pyramidal neurons.
HDAC activity is required for BDNF to increase quantal neurotransmitter release and dendritic spine density in CA1 pyramidal neurons.
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DOI：
10.1002/hipo.20990
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发表时间：
2012-07
期刊：
影响因子：
3.5
通讯作者：
Pozzo-Miller, Lucas
中科院分区：
文献类型：
--
作者：
Calfa, Gaston;Chapleau, Christopher A.;Campbell, Susan;Inoue, Takafumi;Morse, Sarah J.;Lubin, Farah D.;Pozzo-Miller, Lucas
关键词：
参与突触强化和形成的分子机制包括通过不改变遗传密码本身的表观遗传修饰激活和抑制特定基因或基因子集。组蛋白乙酰化介导的染色质修饰对海马兴奋性突触的突触可塑性和海马依赖性记忆的形成至关重要。脑源性神经营养因子（brain-derived neurotrophic factor，BDNF）在突触可塑性和行为适应中起着重要作用，因此在突触可塑性和海马依赖性记忆形成过程中，BDNF基因的调控受到组蛋白乙酰化改变的影响也就不足为奇了。BDNF对树突棘和量子递质释放的影响是否需要组蛋白修饰仍然不太清楚。通过使用两种不同的组蛋白去乙酰化酶（HDAC）的抑制剂，我们在这里描述，它们的活性是必需的BDNF增加树突棘密度和兴奋性量子递质释放到海马切片培养的CA 1锥体神经元。这些结果表明，组蛋白乙酰化/去乙酰化是BDNF调节海马突触的关键步骤。因此，突触形成和功能的表观遗传调节机制是改善与认知和记忆缺陷相关的智力残疾和神经退行性疾病症状的新靶点。
Molecular mechanisms involved in the strengthening and formation of synapses include the activation and repression of specific genes or subsets of genes by epigenetic modifications that do not alter the genetic code itself. Chromatin modifications mediated by histone acetylation have been shown to be critical for synaptic plasticity at hippocampal excitatory synapses and hippocampal-dependent memory formation. Considering that brain-derived neurotrophic factor (BDNF) plays an important role in synaptic plasticity and behavioral adaptations, it is not surprising that regulation of this gene is subject to histone acetylation changes during synaptic plasticity and hippocampal-dependent memory formation. Whether the effects of BDNF on dendritic spines and quantal transmitter release require histone modifications remains less known. By using two different inhibitors of histone deacetylases (HDAC), we describe here that their activity is required for BDNF to increase dendritic spine density and excitatory quantal transmitter release onto CA1 pyramidal neurons in hippocampal slice cultures. These results suggest that histone acetylation/deacetylation is a critical step in the modulation of hippocampal synapses by BDNF. Thus, mechanisms of epigenetic modulation of synapse formation and function are novel targets to consider for the amelioration of symptoms of intellectual disabilities and neurodegenerative disorders associated with cognitive and memory deficits.
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影响因子：
64.8
作者：
Hubbert, C;Guardiola, A;Yao, TP
通讯作者：
Yao, TP
DOI：
10.1523/jneurosci.0097-09.2009
发表时间：
2009-06-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Akhtar MW;Raingo J;Nelson ED;Montgomery RL;Olson EN;Kavalali ET;Monteggia LM
通讯作者：
Monteggia LM
DOI：
10.1523/jneurosci.1786-08.2008
发表时间：
2008-10-15
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Lubin FD;Roth TL;Sweatt JD
通讯作者：
Sweatt JD
影响因子：
5.3
作者：
Boda, B;Alberi, S;Muller, D
通讯作者：
Muller, D
影响因子：
7.6
作者：
Ou, LC;Gean, PW
通讯作者：
Gean, PW