Molecular Neuropathology of Astrocytes and Oligodendrocytes in Alcohol Use Disorders.
Molecular Neuropathology of Astrocytes and Oligodendrocytes in Alcohol Use Disorders.
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DOI：
10.3389/fnmol.2018.00078
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发表时间：
2018
影响因子：
4.8
通讯作者：
Miguel-Hidalgo JJ
中科院分区：
文献类型：
--
作者：
Miguel-Hidalgo JJ
尸检研究揭示了慢性酒精滥用或依赖受试者前额叶皮质（PFC）灰质和白色质（GM和WM）中星形胶质细胞和少突胶质细胞的结构和分子改变。这些神经胶质细胞的变化似乎是平行的，并可能在很大程度上解释使用神经影像学技术检测到的结构和功能的变化与酒精使用障碍（AUDs）的主题。此外，由于星形胶质细胞和少突胶质细胞在神经传递和信号传导中的关键作用，这些细胞很可能是支持PFC和相关互连脑区之间酒精中毒相关连接障碍的分子机制的主要参与者。神经胶质介导的酒精相关脑损伤的病因可能是多因素的，因为代谢、激素、肝脏和血液动力学因素以及乙醇或其代谢产物的直接作用有可能破坏神经胶质神经生物学的不同方面。对酒精中毒动物模型和死后人脑的研究发现，星形胶质细胞标志物在大量暴露于乙醇或酒精戒断过程中发生了变化，如间隙连接蛋白、谷氨酸转运蛋白或与谷氨酸和γ-氨基丁酸（GABA）代谢相关的酶。这些蛋白质及其调控通路的改变不仅会导致GM神经元功能障碍，而且会干扰WM轴突传递冲动的能力。此外，酒精中毒改变星形胶质细胞和髓鞘蛋白和少突胶质细胞转录因子的表达，这些转录因子对WM和GM中髓鞘的维持和可塑性很重要。这些变化伴随着表观遗传DNA和组蛋白修饰以及调节性microRNA（miRNAs）的改变，这些改变可能导致基因表达和蛋白质翻译的严重干扰。关于星形胶质细胞和少突胶质细胞之间的相互作用的知识也是可用的，不仅在朗维尔节点（NR），而且在基于间隙连接的星形胶质细胞-少突胶质细胞接触和其他形式的细胞间通讯中，现在被认为是髓鞘的维持和形成的关键。星形胶质细胞和少突胶质细胞之间的密切相互作用也表明，基于特定神经胶质细胞类型病理学的酒精中毒治疗将需要更好地了解不同细胞类型之间的分子相互作用，以及考虑使用组合分子方法进行更有效治疗的可能性。
Postmortem studies reveal structural and molecular alterations of astrocytes and oligodendrocytes in both the gray and white matter (GM and WM) of the prefrontal cortex (PFC) in human subjects with chronic alcohol abuse or dependence. These glial cellular changes appear to parallel and may largely explain structural and functional alterations detected using neuroimaging techniques in subjects with alcohol use disorders (AUDs). Moreover, due to the crucial roles of astrocytes and oligodendrocytes in neurotransmission and signal conduction, these cells are very likely major players in the molecular mechanisms underpinning alcoholism-related connectivity disturbances between the PFC and relevant interconnecting brain regions. The glia-mediated etiology of alcohol-related brain damage is likely multifactorial since metabolic, hormonal, hepatic and hemodynamic factors as well as direct actions of ethanol or its metabolites have the potential to disrupt distinct aspects of glial neurobiology. Studies in animal models of alcoholism and postmortem human brains have identified astrocyte markers altered in response to significant exposures to ethanol or during alcohol withdrawal, such as gap-junction proteins, glutamate transporters or enzymes related to glutamate and gamma-aminobutyric acid (GABA) metabolism. Changes in these proteins and their regulatory pathways would not only cause GM neuronal dysfunction, but also disturbances in the ability of WM axons to convey impulses. In addition, alcoholism alters the expression of astrocyte and myelin proteins and of oligodendrocyte transcription factors important for the maintenance and plasticity of myelin sheaths in WM and GM. These changes are concomitant with epigenetic DNA and histone modifications as well as alterations in regulatory microRNAs (miRNAs) that likely cause profound disturbances of gene expression and protein translation. Knowledge is also available about interactions between astrocytes and oligodendrocytes not only at the Nodes of Ranvier (NR), but also in gap junction-based astrocyte-oligodendrocyte contacts and other forms of cell-to-cell communication now understood to be critical for the maintenance and formation of myelin. Close interactions between astrocytes and oligodendrocytes also suggest that therapies for alcoholism based on a specific glial cell type pathology will require a better understanding of molecular interactions between different cell types, as well as considering the possibility of using combined molecular approaches for more effective therapies.
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影响因子：
6.2
作者：
Alfonso-Loeches, Silvia;Pascual, Maria;Guerri, Consuelo
通讯作者：
Guerri, Consuelo
影响因子：
6.2
作者：
Cui, W;Allen, ND;Clark, AJ
通讯作者：
Clark, AJ
DOI：
10.1016/s0165-3806(02)00512-6
发表时间：
2002-11-15
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Bichenkov, E;Ellingson, JS
通讯作者：
Ellingson, JS
影响因子：
3.6
作者：
Coleman, Leon Garland, Jr.;Liu, Wen;Oguz, Ipek;Styner, Martin;Crews, Fulton T.
通讯作者：
Crews, Fulton T.
影响因子：
3.7
作者：
Collins MA;Neafsey EJ
通讯作者：
Neafsey EJ