Wieczorek Lindsay, Fish Eric W, O'Leary-Moore Shonagh K, Parnell Scott E, Sulik Kathleen K
Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC, USA.
Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC, USA.
Alcohol. 2015 May;49(3):207-17. doi: 10.1016/j.alcohol.2015.01.005. Epub 2015 Jan 26.
The range of defects that fall within fetal alcohol spectrum disorder (FASD) includes persistent behavioral problems, with anxiety and depression being two of the more commonly reported issues. Previous studies of rodent FASD models suggest that interference with hypothalamic-pituitary-adrenal (HPA) axis structure and/or function may be the basis for some of the prenatal alcohol (ethanol) exposure (PAE)-induced behavioral abnormalities. Included among the previous investigations are those illustrating that maternal alcohol treatment limited to very early stages of pregnancy (i.e., gestational day [GD]7 in mice; equivalent to the third week post-fertilization in humans) can cause structural abnormalities in areas such as the hypothalamus, pituitary gland, and other forebrain regions integral to controlling stress and behavioral responses. The current investigation was designed to further examine the sequelae of prenatal alcohol insult at this early time period, with particular attention to HPA axis-associated functional changes in adult mice. The results of this study reveal that GD7 PAE in mice causes HPA axis dysfunction, with males and females showing elevated corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, respectively, following a 15-min restraint stress exposure. Males also showed elevated CORT levels following an acute alcohol injection of 2.0 g/kg, while females displayed blunted ACTH levels. Furthermore, analysis showed that anxiety-like behavior was decreased after GD7 PAE in female mice, but was increased in male mice. Collectively, the results of this study show that early gestational alcohol exposure in mice alters long-term HPA axis activity and behavior in a sexually dimorphic manner.
胎儿酒精谱系障碍（FASD）所涵盖的缺陷范围包括持续性行为问题，焦虑和抑郁是其中报告较为普遍的两个问题。先前对啮齿动物FASD模型的研究表明，下丘脑 - 垂体 - 肾上腺（HPA）轴结构和/或功能受到干扰可能是产前酒精（乙醇）暴露（PAE）所致某些行为异常的基础。先前的研究包括那些表明仅在妊娠极早期（即小鼠妊娠第7天；相当于人类受精后第三周）给予母体酒精处理可导致下丘脑、垂体以及其他对控制应激和行为反应至关重要的前脑区域出现结构异常的研究。当前的研究旨在进一步探究在此早期阶段产前酒精损伤的后果，特别关注成年小鼠中与HPA轴相关的功能变化。这项研究的结果显示，小鼠妊娠第7天的PAE会导致HPA轴功能障碍，在15分钟的束缚应激暴露后，雄性和雌性小鼠的皮质酮（CORT）和促肾上腺皮质激素（ACTH）水平分别升高。雄性小鼠在急性注射2.0 g/kg酒精后CORT水平也升高，而雌性小鼠的ACTH水平则降低。此外，分析表明，妊娠第7天的PAE后，雌性小鼠的焦虑样行为减少，而雄性小鼠的焦虑样行为增加。总体而言，这项研究的结果表明，小鼠妊娠早期酒精暴露会以性别差异的方式改变长期的HPA轴活动和行为。
