Decreased expression of NEFH and PCP4/PEP19 in the prefrontal cortex of alcoholics
Decreased expression of NEFH and PCP4/PEP19 in the prefrontal cortex of alcoholics
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DOI：
10.1016/j.neures.2004.04.002
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发表时间：
2004-08-01
影响因子：
2.9
通讯作者：
Kato, T
中科院分区：
文献类型：
--
作者：
Iwamoto, K;Bundo, M;Kato, T
酒精中毒患者表现出对酒精的行为适应，如耐受性、依赖性和成瘾性。这些改变对乙醇的行为反应的分子机制在很大程度上还不清楚。我们对酗酒者的死后前额皮质进行了寡核苷酸微阵列分析。在大约12，000个基因中，与对照组相比，共有79个基因在酗酒者中表现出差异表达变化，其中包括54个上调和25个下调基因。在具有广泛生物学功能的基因中观察到酗酒者的表达改变。值得注意的发现是酗酒者中髓鞘相关基因和分子伴侣的上调。在鉴定的基因中，进一步检查了NEFH和PCP 41 PEP 19的表达降低。NEFH编码神经元中的神经丝蛋白组分。PCP 41 PEP 19编码的蛋白参与钙信号和神经元凋亡。通过实时定量RT-PCR证实了在微阵列分析中观察到的酗酒者的下调，并且在酗酒者的死后脑的独立组中也得到了证实。本研究结果可能为从分子水平上理解乙醇诱导的行为反应改变的机制提供一些见解。(C)2004年爱思唯尔爱尔兰有限公司和日本神经科学学会。All rights reserved.
Patients with alcoholism exhibit behavioral adaptations to ethanol such as tolerance, dependence, and addiction. Molecular mechanisms that underlie these altered behavioral responses to ethanol are largely unclear. We have performed oligonucleotide microarray analysis in postmortem prefrontal cortices of alcoholics. Among about 12,000 genes represented on microarray, a total of 79 genes showed differential expression changes in alcoholics compared with control subjects, consisting of 54 up- and 25 down-regulated genes. Altered expressions in alcoholics were observed in genes having a wide range of biological functions. The remarkable findings were up-regulation of myelin-related genes and molecular chaperones in alcoholics. Among the genes identified, decreased expressions of NEFH and PCP41PEP19 were further examined. NEFH encodes a component of neurofilament protein in neurons. PCP41PEP19 encodes protein involved in calcium signaling and neuronal apoptosis. Observation of their down-regulations in alcoholics in microarray analysis was confirmed by real-time quantitative RT-PCR, and was also confirmed in the independent set of postmortem brains of alcoholics. The present results may provide some insights into understanding the mechanism of ethanol-induced altered behavioral responses at the molecular level. (C) 2004 Elsevier Ireland Ltd and The Japan Neuroscience Society. All rights reserved.