Fidalgo Sara, Skipper Charlotte, Takyi Abigail, McIver Aisling, Tsiligkaridis Theodoros, Quadir Angela, Gard Paul R
School of Pharmacy and Biomolecular Sciences, University of Brighton, Moulsecoomb, Brighton, BN2 4GJ, UK.
Behav Brain Res. 2017 Jun 30;329:140-147. doi: 10.1016/j.bbr.2017.04.042. Epub 2017 Apr 27.
Prenatal ethanol exposure (PAE) in humans results in a spectrum of disorders including deficits in learning and memory. Animal models to date have typically used high ethanol doses but have not identified the biochemical changes underlying the cognitive deficit. This study used treatment of mouse breeding harems with 5% ethanol via drinking water throughout pregnancy and lactation and explored the behavioural consequences in the progeny at 3-6 months of age using the open field test, novel object recognition test and elevated plus maze to measure anxiety and memory consolidation. The effects of angiotensin IV on behaviour of the progeny were also determined. The results indicated that PAE increased anxiety-like behaviour as determined in the open field test in male but not female progeny. In control animals, angiotensin IV enhanced memory consolidation in males, but this effect was abolished by PAE. The abolition of the pro-cognitive effect of angiotensin IV was not a consequence of increased anxiety, and there was some evidence of a long-lasting anxiolytic effect of angiotensin IV in the male PAE progeny. These results suggest that PAE may act via alteration of the actions of the brain renin-angiotensin system to impair memory consolidation, but these effects may be partially sex-dependent.
人类孕期乙醇暴露(PAE)会导致一系列疾病,包括学习和记忆缺陷。迄今为止,动物模型通常使用高剂量乙醇,但尚未确定认知缺陷背后的生化变化。本研究在整个怀孕和哺乳期通过饮用水对小鼠繁殖群体进行5%乙醇处理,并在3至6月龄后代中使用旷场试验、新物体识别试验和高架十字迷宫来测量焦虑和记忆巩固,以此探究行为后果。还确定了血管紧张素IV对后代行为的影响。结果表明,如在旷场试验中所确定的,PAE增加了雄性而非雌性后代的焦虑样行为。在对照动物中,血管紧张素IV增强了雄性的记忆巩固,但PAE消除了这种作用。血管紧张素IV促认知作用的消除并非焦虑增加的结果,并且有一些证据表明血管紧张素IV对雄性PAE后代有持久的抗焦虑作用。这些结果表明,PAE可能通过改变脑肾素-血管紧张素系统的作用来损害记忆巩固,但这些影响可能部分取决于性别。