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神经管形成期急性酒精暴露:对青春期C57BL/6J小鼠行为和脑结构的影响

Acute alcohol exposure during neurulation: Behavioral and brain structural consequences in adolescent C57BL/6J mice.

作者信息

Fish E W, Holloway H T, Rumple A, Baker L K, Wieczorek L A, Moy S S, Paniagua B, Parnell S E

机构信息

Bowles Center for Alcohol Studies (EWF, HTH, LKB, LAW, SEP), Department of Cell Biology and Physiology (SEP), Department of Psychiatry (AMR, SSM, BP), and Carolina Institute for Developmental Disabilities (SSM, BP, SEP), University of North Carolina, Chapel Hill, NC 27599, United States.

Bowles Center for Alcohol Studies (EWF, HTH, LKB, LAW, SEP), Department of Cell Biology and Physiology (SEP), Department of Psychiatry (AMR, SSM, BP), and Carolina Institute for Developmental Disabilities (SSM, BP, SEP), University of North Carolina, Chapel Hill, NC 27599, United States.

出版信息

Behav Brain Res. 2016 Sep 15;311:70-80. doi: 10.1016/j.bbr.2016.05.004. Epub 2016 May 13.

Abstract

Prenatal alcohol exposure (PAE) can induce physical malformations and behavioral abnormalities that depend in part on thedevelopmental timing of alcohol exposure. The current studies employed a mouse FASD model to characterize the long-term behavioral and brain structural consequences of a binge-like alcohol exposure during neurulation; a first-trimester stage when women are typically unaware that they are pregnant. Time-mated C57BL/6J female mice were administered two alcohol doses (2.8g/kg, four hours apart) or vehicle starting at gestational day 8.0. Male and female adolescent offspring (postnatal day 28-45) were then examined for motor activity (open field and elevated plus maze), coordination (rotarod), spatial learning and memory (Morris water maze), sensory motor gating (acoustic startle and prepulse inhibition), sociability (three-chambered social test), and nociceptive responses (hot plate). Regional brain volumes and shapes were determined using magnetic resonance imaging. In males, PAE increased activity on the elevated plus maze and reduced social novelty preference, while in females PAE increased exploratory behavior in the open field and transiently impaired rotarod performance. In both males and females, PAE modestly impaired Morris water maze performance and decreased the latency to respond on the hot plate. There were no brain volume differences; however, significant shape differences were found in the cerebellum, hypothalamus, striatum, and corpus callosum. These results demonstrate that alcohol exposure during neurulation can have functional consequences into adolescence, even in the absence of significant brain regional volumetric changes. However, PAE-induced regional shape changes provide evidence for persistent brain alterations and suggest alternative clinical diagnostic markers.

摘要

产前酒精暴露(PAE)可诱发身体畸形和行为异常,部分取决于酒精暴露的发育时间。当前研究采用小鼠胎儿酒精谱系障碍(FASD)模型,以表征在神经胚形成期(女性通常在此孕早期阶段未意识到自己已怀孕)进行类似暴饮的酒精暴露所产生的长期行为和脑结构后果。从妊娠第8.0天开始,对按时间交配的C57BL/6J雌性小鼠给予两种酒精剂量(2.8克/千克,间隔4小时)或赋形剂。然后对雄性和雌性青春期后代(出生后第28 - 45天)进行运动活动(旷场试验和高架十字迷宫试验)、协调性(转棒试验)、空间学习和记忆(莫里斯水迷宫试验)、感觉运动门控(听觉惊吓和前脉冲抑制)、社交能力(三室社交试验)以及伤害性反应(热板试验)的检测。使用磁共振成像确定脑区体积和形状。在雄性中,PAE增加了高架十字迷宫试验中的活动,并降低了对社交新奇性的偏好,而在雌性中,PAE增加了旷场试验中的探索行为,并短暂损害了转棒试验表现。在雄性和雌性中,PAE均适度损害了莫里斯水迷宫试验表现,并缩短了热板试验中的反应潜伏期。脑体积没有差异;然而,在小脑、下丘脑、纹状体和胼胝体中发现了显著的形状差异。这些结果表明,即使在没有明显脑区体积变化的情况下,神经胚形成期的酒精暴露也会对青春期产生功能影响。然而,PAE诱导的区域形状变化为脑的持续改变提供了证据,并提示了替代的临床诊断标志物。

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