Clinical and animal studies show maternal alcohol consumption during pregnancy causes in offspring persistent alterations in neuroimmune and neurochemical systems known to increase alcohol drinking and related behaviors. Studies in lateral hypothalamus (LH) demonstrate in adolescent offspring that maternal oral administration of ethanol stimulates the neuropeptide, melanin-concentrating hormone (MCH), together with the inflammatory chemokine C-C motif ligand 2 (CCL2) and its receptor CCR2 which are increased in most MCH neurons. These effects, consistently stronger in females than males, are detected in embryos, not only in LH but hypothalamic neuroepithelium (NEP) along the third ventricle where neurons are born and CCL2 is stimulated within radial glia progenitor cells and their laterally projecting processes that facilitate MCH neuronal migration toward LH. With ethanol's effects similarly produced by maternal peripheral CCL2 administration and blocked by CCR2 antagonist, we tested here using in utero intracerebroventricular (ICV) injections whether CCL2 acts locally within the embryonic NEP. After ICV injection of CCL2 (0.1 µg/µl) on embryonic day 14 (E14) when neurogenesis peaks, we observed in embryos just before birth (E19) a significant increase in endogenous CCL2 within radial glia cells and their processes in NEP. These auto-regulatory effects, evident only in female embryos, were accompanied by increased density of CCL2 and MCH neurons in LH, more strongly in females than males. These results support involvement of embryonic CCL2/CCR2 neuroimmune system in radial glia progenitor cells in mediating sexually dimorphic effects of maternal challenges such as ethanol on LH MCH neurons that colocalize CCL2 and CCR2.

中文翻译：

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大鼠胚胎第三心室注射 CCL2 刺激神经上皮放射状胶质祖细胞中的 CCL2/CCR2 神经免疫系统：与下丘脑外侧肽神经元的性二态性和刺激作用的关系。


临床和动物研究表明，母亲在怀孕期间饮酒会导致后代神经免疫和神经化学系统持续改变，已知会增加饮酒和相关行为。下丘脑外侧 (LH) 的研究表明，在青少年后代中，母体口服乙醇会刺激神经肽、黑色素浓缩激素 (MCH)，以及炎症趋化因子 CC 基序配体 2 (CCL2) 及其受体 CCR2，这些物质在大多数情况下都会增加。 MCH 神经元。这些效应在女性中始终强于男性，在胚胎中也可检测到，不仅在 LH 中，而且在第三脑室的下丘脑神经上皮 (NEP) 中也可检测到，神经元在第三脑室中诞生，CCL2 在放射状胶质祖细胞及其促进 MCH 的横向突出过程中受到刺激。神经元向 LH 迁移。由于乙醇的作用类似地通过母体外周 CCL2 给药产生并被 CCR2 拮抗剂阻断，我们在这里使用子宫内脑室内 (ICV) 注射测试 CCL2 是否在胚胎 NEP 内局部起作用。在胚胎第 14 天 (E14)，即神经发生高峰时，ICV 注射 CCL2 (0.1 µg/µl) 后，我们在出生前 (E19) 的胚胎中观察到，放射状胶质细胞内的内源性 CCL2 及其在 NEP 中的过程显着增加。这些自动调节效应仅在雌性胚胎中明显，并伴随着 LH 中 CCL2 和 MCH 神经元密度的增加，在雌性胚胎中比雄性更强烈。这些结果支持放射状胶质祖细胞中的胚胎 CCL2/CCR2 神经免疫系统参与介导母体挑战（例如乙醇）对 CCL2 和 CCR2 共定位的 LH MCH 神经元的性二态性影响。