Prenatal Alcohol Exposure in Rats Diminish Postnatal Cxcl16 Chemokine Ligand Brain Expression

Maternal ethanol consumption during pregnancy is one of the main causes of Neurodevelopmental disorders (NDD). Prenatal alcohol exposure (PAE) produces several adverse manifestations. Even low or moderate intake has been associated with long lasting behavioral and cognitive impairment in offspring. In this study we examined the gene expression profile in the rat nucleus accumbens using microarrays, comparing animals prenatally exposed to ethanol and controls. The microarray gene expression showed an overall downward regulatory effect of PAE. Gene cluster analysis reveals that the main affected gene groups are related to transcription regulation, transcription factors and homeobox genes. We focus on the expression of the C-X-C motif chemokine ligand 16 (Cxcl16) which was differentially expressed. There is a significant reduction in the expression of this chemokine throughout the brain under PAE conditions, evidenced here by qPCR and immunohistochemistry. Chemokines are involved in neuroprotection and implicated in alcohol-induced brain damaged and neuroinflammation in the developing CNS, therefore, the significance of the overall decrease in Cxcl16 expression in the brain as a consequence of PAE, may reflect a reduced ability to neuroprotection against subsequent conditions, such as excitotoxic damage, inflammatory processes or even hypoxic-ischemic insult.妊娠期母体乙醇摄入是引发神经发育障碍（Neurodevelopmental Disorders, NDD）的主要诱因之一。产前酒精暴露（Prenatal Alcohol Exposure, PAE）可引发多种不良表现，即便仅为低剂量或中等剂量的乙醇摄入，也会对子代造成长期的行为与认知功能损伤。本研究采用微阵列（microarray）技术，对比了产前暴露于乙醇的大鼠与对照组大鼠的伏隔核基因表达谱。微阵列基因表达分析结果显示，PAE对基因表达整体呈现下调调控作用。基因聚类分析表明，受影响最为显著的基因簇主要与转录调控、转录因子及同源框基因相关。本研究重点关注了差异表达的C-X-C基序趋化因子配体16（C-X-C motif chemokine ligand 16, Cxcl16）的表达情况。经定量聚合酶链式反应（quantitative polymerase chain reaction, qPCR）与免疫组织化学实验验证，PAE状态下该趋化因子在全脑的表达量均显著降低。趋化因子参与神经保护过程，且与发育中的中枢神经系统（central nervous system, CNS）内酒精诱导的脑损伤及神经炎症密切相关。因此，PAE导致的全脑Cxcl16表达整体下调，或反映了机体针对后续损伤（如兴奋性毒性损伤、炎症过程乃至缺血缺氧性损伤）的神经保护能力有所下降。