Age-related alterations in histone deacetylase expression in Purkinje neurons of ethanol-fed rats.
Age-related alterations in histone deacetylase expression in Purkinje neurons of ethanol-fed rats.
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DOI：
10.1016/j.brainres.2017.08.026
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发表时间：
2017-11-15
期刊：
影响因子：
2.9
通讯作者：
Dlugos CA
中科院分区：
文献类型：
--
作者：
Khurana A;Dlugos CA
乙醇和AGE诱导的浦肯野神经元(PN)的病理可能是由组蛋白脱乙酰酶(HDACs)引起的，组蛋白脱乙酰酶通过DNA卷曲来抑制转录。本研究的目的是研究1类和IIa类HDAC在PN中的表达模式，以及衰老和酒精对PN中HDAC密度和组蛋白乙酰化的影响。将98只8月龄大鼠(30只/只)以液体乙醇、液体对照或大鼠饲料喂养10、20或40周(30只/只)。在这些大鼠的组织切片上进行双重免疫细胞化学标记，使用了针对HDAC亚型或乙酰化组蛋白的抗体，以及用于PN的标记物Calbindin。还测量了荧光强度。结果显示，酒精对HDAC 2、3和7的密度无明显影响，但随着年龄的增长，HDAC(4，5，7)Pn的磷酸化密度和表达HDAC 7的PN核的密度随年龄增加而显著增加。这项研究提供了关于哪些HDAC通常在PN中表达的独特数据，并表明老化而不是长时间的酒精表达改变了这里所研究的HDAC的表达。这些结果还表明，长期饮酒可能会抑制PN中的组蛋白去乙酰化。
Ethanol and age-induced pathologies of the Purkinje neuron (PN) may result from histone deacetylases (HDACs), enzymes which repress transcription through coiling of the DNA. The purposes of this study were to investigate expression patterns of Class 1 and IIa HDACs in PN and the effects of aging and alcohol on the density of HDACs and histone acetylation in PN. Ninety, eight month old rats (30/diet) were fed a liquid ethanol, liquid control, or rat chow diet for 10, 20, or 40 weeks (30/ treatment duration). Double immunocytochemical labeling on tissue sections from these rats used antibodies against HDAC isoforms or acetylated histones, and calbindin, a marker for PN. Fluorescent intensities were also measured. Results showed a significant age but not an alcohol-related decrease in the densities of HDACs 2, 3, and 7. In contrast, there were age related-increases in the densities of phosphorylated form of HDAC (4,5,7) PN and in PN nuclei expressing HDAC 7. There were also a trend towards ethanol-induced inhibition of acetylation as the density of AH2b PN nuclei and AH3 and AH2b fluorescent intensity was significantly lower in the EF compared to the PF rats. This study presents unique data concerning which HDACs are commonly expressed in PN and indicates that aging rather than lengthy alcohol expression alters expression of the HDACs studied here. These results also suggest that lengthy ethanol consumption may inhibit histone deacetylation in PN.
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