Reduced connexin 43 immunolabeling in the orbitofrontal cortex in alcohol dependence and depression.
Reduced connexin 43 immunolabeling in the orbitofrontal cortex in alcohol dependence and depression.
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DOI：
10.1016/j.jpsychires.2014.04.007
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发表时间：
2014-08
影响因子：
4.8
通讯作者：
Stockmeier, Craig A.
中科院分区：
文献类型：
--
作者：
Miguel-Hidalgo, Jose Javier;Wilson, Barbara A.;Hussain, Syed;Meshram, Ashish;Rajkowska, Grazyna;Stockmeier, Craig A.
关键词：
抑郁症和酒精中毒患者眼眶前额叶皮质(OFC)胶质细胞密度降低和某些星形胶质细胞蛋白水平降低，这两种疾病经常并存。这些退行性变化还可能涉及星形胶质细胞之间通过缝隙连接和半脑沟进行的通讯，后者在神经传递中起着重要的调节作用。我们测定了抑郁症、酒精中毒或抑郁症/酒精中毒共病患者与非精神病患者OFC中星形胶质细胞缝隙连接/半突触的主要蛋白亚基--连接蛋白43(Cx43)的水平和形态免疫染色参数。对23例重度抑郁障碍(MDD)患者、16例酒精依赖患者、13例MDD合并酒精依赖患者和20例精神正常对照患者的尸脑标本进行蛋白质印迹分析，以确定Cx43的水平。组织切片测量Cx43免疫反应面积分数、免疫反应斑点密度和平均大小。与对照组相比，三个精神病组的Cx43水平显著下降，降幅超过60%。在所有精神病组中，免疫反应面积分数和免疫反应斑点大小均减少，但Cx43免疫反应斑点密度仅在酒精依赖者中减少。在精神病受试者中，自杀和非自杀患者之间的Cx43水平和免疫染色没有发现差异。目前的数据提示，抑郁症和酒精中毒患者OFC功能障碍伴随着缝隙连接蛋白Cx43水平的降低，以及仅在酒精中毒时的Cx43免疫反应斑点密度降低，提示在这些疾病的病理生理学中，缝隙连接或基于半通道的通讯发生了改变。
Reduced density of glial cells and low levels of some astrocyte proteins have been described in the orbitofrontal cortex (OFC) in depression and alcoholism, two disorders often comorbid. These regressive changes may also involve the communication between astrocytes via gap junctions and hemichannels, which play important regulatory roles in neurotransmission. We determined levels and morphological immunostaining parameters of connexin 43 (Cx43), the main protein subunit of astrocyte gap junctions/hemichannels, in the OFC of subjects with depression, alcoholism or comorbid depression/alcoholism as compared to non-psychiatric subjects. Postmortem brain samples from 23 subjects with major depressive disorder (MDD), 16 with alcohol dependence, 13 with comorbid MDD and alcohol dependence, and 20 psychiatrically-normal comparison subjects were processed for western blots to determine Cx43 levels. Area fraction of Cx43 immunoreactivity, and density and average size of immunoreactive puncta were measured in histological sections. There was a significant, larger than 60 percent decrease in Cx43 level in the three psychiatric groups as compared to controls. Area fraction of immunoreactivity and immunoreactive punctum size were reduced in all psychiatric groups, but Cx43-immunoreactive puncta density was reduced only in alcohol-dependent subjects. Among psychiatric subjects, no difference in Cx43 levels or immunostaining was found between suicides and non-suicides. The present data suggest that dysfunction of the OFC is accompanied by reduction in the levels of gap junction protein Cx43 in depression and alcoholism, and reduction in density of Cx43 immunoreactive puncta only in alcoholism, pointing to altered gap junction or hemichannel-based communication in the pathophysiology of those disorders.
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影响因子：
3.4
作者：
Gonzalez, Vivian M.
通讯作者：
Gonzalez, Vivian M.
影响因子：
3.5
作者：
Figiel, Maciej;Allritz, Claudia;Engele, Juergen
通讯作者：
Engele, Juergen
DOI：
10.1097/paf.0b013e31827bf67f
发表时间：
2013-03-01
影响因子：
1
作者：
Huang, Quan-Yong;Li, Xue-Fang;Liu, Shui-Ping
通讯作者：
Liu, Shui-Ping
影响因子：
11
作者：
通讯作者：
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影响因子：
2
作者：
GUNDERSEN, HJG
通讯作者：
GUNDERSEN, HJG