Elibol-Can Birsen, Dursun Ilknur, Telkes Ilknur, Kilic Ertugrul, Canan Sinan, Jakubowska-Dogru Ewa
Department of Biological Sciences, Middle East Technical University, Ankara, 06531, Turkey.
Dev Neurobiol. 2014 May;74(5):498-513. doi: 10.1002/dneu.22143. Epub 2013 Dec 3.
Ethanol is known as a potent teratogen having adverse effects on brain and behavior. However, some of the behavioral deficits caused by fetal alcohol exposure and well expressed in juveniles ameliorate with maturation may suggest some kind of functional recovery occurring during postnatal development. The aim of this study was to reexamine age-dependent behavioral impairments in fetal-alcohol rats and to investigate the changes in neurogenesis and gross morphology of the hippocampus during a protracted postnatal period searching for developmental deficits and/or delays that would correlate with behavioral impairments in juveniles and for potential compensatory processes responsible for their amelioration in adults. Ethanol was delivered to the pregnant dams by intragastric intubation throughout 7-21 gestation days at daily dose of 6 g/kg. Isocaloric intubation and intact control groups were included. Locomotor activity, anxiety, and spatial learning tasks were applied to juvenile and young-adult rats from all groups. Unbiased stereological estimates of hippocampal volumes, the total number of pyramidal and granular cells, and double cortin expressing neurons were carried out for postnatal days (PDs) PD1, PD10, PD30, and PD60. Alcohol insult during second trimester equivalent caused significant deficits in the spatial learning in juvenile rats; however, its effect on hippocampal morphology was limited to a marginally lower number of granular cells in dentate gyrus (DG) on PD30. Thus, initial behavioral deficits and the following functional recovery in fetal-alcohol subjects may be due to more subtle plastic changes within the hippocampal formation but also in other structures of the extended hippocampal circuit. Further investigation is required.
乙醇是一种已知的强效致畸剂,对大脑和行为有不良影响。然而,胎儿酒精暴露所导致的一些行为缺陷在幼年时表现明显,但随着成熟会有所改善,这可能表明在出生后发育过程中发生了某种功能恢复。本研究的目的是重新审视胎儿酒精暴露大鼠中与年龄相关的行为损伤,并在延长的出生后时期研究海马体神经发生和大体形态的变化,寻找与幼年行为损伤相关的发育缺陷和/或延迟,以及负责成年期改善的潜在补偿过程。在妊娠第7至21天,通过胃内插管每天以6 g/kg的剂量给怀孕母鼠喂食乙醇。纳入等热量插管和完整对照组。对所有组的幼年和年轻成年大鼠进行运动活动、焦虑和空间学习任务测试。对出生后第1天、第10天、第30天和第60天的大鼠进行无偏立体学估计,测量海马体体积、锥体和颗粒细胞总数以及双皮质素表达神经元数量。孕中期同等程度的酒精损伤导致幼年大鼠空间学习能力显著缺陷;然而,其对海马体形态的影响仅限于出生后第30天齿状回颗粒细胞数量略少。因此,胎儿酒精暴露个体最初的行为缺陷及随后的功能恢复可能是由于海马结构内以及扩展海马回路的其他结构中更细微的可塑性变化。需要进一步研究。