Alpha-fetoprotein (AFP) modulates the effect of serum albumin on brain development by restraining the neurotrophic effect of oleic acid
Alpha-fetoprotein (AFP) modulates the effect of serum albumin on brain development by restraining the neurotrophic effect of oleic acid
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DOI：
10.1016/j.brainres.2015.07.021
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发表时间：
2015-10-22
期刊：
影响因子：
2.9
通讯作者：
Medina, Jose M.
中科院分区：
文献类型：
--
作者：
Garcia-Garcia, Alejandro G.;Polo-Hernandez, Erica;Medina, Jose M.
我们之前已经表明，血清白蛋白通过星形胶质细胞对油酸合成的调节来控制围产期大鼠大脑发育。事实上，星形胶质细胞合成和释放的油酸促进了神经突的生长、神经元的迁移和前瞻性突触的排列。在这项研究中，我们发现甲胎蛋白（AFP）在胚胎发育期间也存在于大脑中，其浓度在E15.5和E19.5时达到峰值。然而，在E19.5后，AFP浓度骤降，同时血清白蛋白浓度急剧上升。在E15.5时，甲胎蛋白出现在大脑的尾侧区域，特别是在这一时期发生分化的大脑区域，如丘脑的丘脑网状核、下丘脑、杏仁核和海马体。在E15.5时，白蛋白未在大脑中检测到，但在E19.5天，白蛋白在脑细胞中大量染色，在相同情况下，白蛋白的分布与AFP非常相似。脑内游离油酸浓度与AFP浓度呈负相关，提示AFP和油酸所激发的信号可能呈负相关。由于油酸的存在而高度表达的轴突生长标志物GAP-43，除了在边缘区和划定底板的区域外，没有与AFP共定位。在体外原代培养和离体胚胎大鼠脑器官型培养中，AFP阻止油酸在神经元中引起的GAP-43表达增加，提示AFP可能调节血清白蛋白对脑发育的影响。(C) 2015年作者。这是一篇基于CC by-nc-nd许可（http://creativecommons.org/licenses/by-nc-nd/4.0/）的开放获取文章。
We have previously shown that serum albumin controls perinatal rat brain development through the regulation of oleic acid synthesis by astrocytes. In fact, oleic acid synthesized and released by astrocytes promoted neurite growth, neuron migration and the arrangement of prospective synapses. In this work we show that alpha-fetoprotein (AFP) is also present in the brain during embryonic development, its concentrations peaking at E15.5 and at E19.5. However, after E19.5 AFP concentrations plummeted concurrently with a sharp increase in serum albumin concentrations. At E15.5, AFP is present in caudal regions of the brain, particularly in brain areas undergoing differentiation during this period, such as the thalamic reticular nucleus of the thalamus, the hypothalamus, the amygdala and the hippocampus. Albumin was not detected in the brain at E15.5 but stained brain cells substantially on day E19.5, showing a very similar distribution to that of AFP under the same circumstances. The concentrations of free oleic acid in the brain were inversely correlated with those of AFP, suggesting that the signals elicited by AFP and oleic acid can be inversely associated. GAP-43, a marker of axonal growth that is highly expressed by the presence of oleic acid, was not co-localized with AFP except in the marginal zone and areas delimiting the subplate. AFP prevented the increase in GAP-43 expression caused by the presence of oleic acid in neurons in primary culture in vitro and in organotypic cultures of embryonic rat brain ex vivo, suggesting that AFP may modulate the effect of serum albumin on brain development. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).