Inhibition of Histone Deacetylase 3 Restores Amyloid-β Oligomer-Induced Plasticity Deficit in Hippocampal CA1 Pyramidal Neurons
Inhibition of Histone Deacetylase 3 Restores Amyloid-β Oligomer-Induced Plasticity Deficit in Hippocampal CA1 Pyramidal Neurons
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DOI：
10.3233/jad-150838
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发表时间：
2016-01-01
影响因子：
4
通讯作者：
Sajikumar, Sreedharan
中科院分区：
文献类型：
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作者：
Krishna, Kumar;Behnisch, Thomas;Sajikumar, Sreedharan
神经退行性疾病如阿尔茨海默病（AD）与表观遗传因素的改变相关，表观遗传因素导致认知能力下降。组蛋白去乙酰化酶3（HDAC3）是已知的学习和记忆的关键表观遗传负调节因子。在这项研究中，衰减的长时程增强淀粉样β寡聚体，其逆转特定HDAC3抑制剂RGFP966，在大鼠CA1锥体神经元使用全细胞电压钳和场记录技术。我们的研究结果提供了第一个证据，即淀粉样蛋白β寡聚体诱导的突触可塑性损伤可以通过抑制单个神经元以及神经元群体中的HDAC3酶来预防，从而将HDAC3鉴定为改善AD相关可塑性损伤的潜在靶点。
Neurodegenerative diseases such as Alzheimer's disease (AD) are associated with alterations in epigenetic factors leading to cognitive decline. Histone deacetylase 3 (HDAC3) is a known critical epigenetic negative regulator of learning and memory. In this study, attenuation of long-term potentiation by amyloid-beta oligomer, and its reversal by specific HDAC3 inhibitor RGFP966, was performed in rat CA1 pyramidal neurons using whole cell voltage-clamp and field recording techniques. Our findings provide the first evidence that amyloid-beta oligomer-induced synaptic plasticity impairment can be prevented by inhibition of HDAC3 enzyme both at the single neuron as well as in a population of neurons, thus identifying HDAC3 as a potential target for ameliorating AD related plasticity impairments.