Protective effects of resveratrol on the inhibition of hippocampal neurogenesis induced by ethanol during early postnatal life
Protective effects of resveratrol on the inhibition of hippocampal neurogenesis induced by ethanol during early postnatal life
复制标题
白藜芦醇对产后早期乙醇诱导的海马神经发生的抑制作用
DOI：
10.1016/j.bbadis.2015.03.009
复制
发表时间：
2015-07-01
影响因子：
6.2
通讯作者：
Fan, Xiaotang
中科院分区：
文献类型：
--
作者：
Xu, Le;Yang, Yang;Fan, Xiaotang
出生后早期乙醇暴露对发育中的海马产生明显的神经毒性作用，并对海马神经发生产生长期影响。白藜芦醇（Resveratrol，RSV）通过促进海马神经元的再生而发挥神经保护作用。然而，RSV对EtOH介导的海马神经发生损伤的影响仍未确定。因此，用RSV预处理小鼠，然后暴露于EtOH，以评估其在海马发育期间对EtOH介导的毒性的保护作用。结果表明，出生后第7天短暂暴露于乙醇导致海马神经发生的显着损害和海马神经前体细胞（NPC）的耗竭。这种作用通过用RSV预处理而减弱。此外，乙醇暴露导致齿状回（DG）的颗粒神经元上的棘密度降低，并且棘表现出较不成熟的形态表型，其特征在于较高比例的棘状棘和较低比例的蘑菇棘。然而，RSV治疗有效地逆转了这些反应。我们进一步证实RSV处理逆转了EtOH诱导的海马pERK和Hesl蛋白水平的下调，这可能与NPC的增殖和维持有关。此外，C17.2 NPC中的EtOH暴露也减少了细胞增殖并激活了凋亡，这可以通过RSV预处理来逆转。总体而言，我们的研究结果表明，RSV预处理保护对EtOH诱导的缺陷，在出生后的小鼠神经发生，因此可能发挥关键作用，防止EtOH介导的毒性在发育中的海马。(C)2015 Elsevier B.V.版权所有。
Ethanol (EtOH) exposure during early postnatal life triggers obvious neurotoxic effects on the developing hippocampus and results in long-term effects on hippocampal neurogenesis. Resveratrol (RSV) has been demonstrated to exert potential neuroprotective effects by promoting hippocampal neurogenesis. However, the effects of RSV on the EtOH-mediated impairment of hippocampal neurogenesis remain undetermined. Thus, mice were pretreated with RSV and were later exposed to EtOH to evaluate its protective effects on EtOH-mediated toxicity during hippocampal development. The results indicated that a brief exposure of EtOH on postnatal day 7 resulted in a significant impairment in hippocampal neurogenesis and a depletion of hippocampal neural precursor cells (NPCs). This effect was attenuated by pretreatment with RSV. Furthermore, EtOH exposure resulted in a reduction in spine density on the granular neurons of the dentate gyrus (DG), and the spines exhibited a less mature morphological phenotype characterized by a higher proportion of stubby spines and a lower proportion of mushroom spines. However, RSV treatment effectively reversed these responses. We further confirmed that RSV treatment reversed the EtOH-induced down-regulation of hippocampal pERK and Hesl protein levels, which may be related to the proliferation and maintenance of NPCs. Furthermore, EtOH exposure in the C17.2 NPCs also diminished cell proliferation and activated apoptosis, which could be reversed by pretreatment of RSV. Overall, our results suggest that RSV pretreatment protects against EtOH-induced defects in neurogenesis in postnatal mice and may thus play a critical role in preventing EtOH-mediated toxicity in the developing hippocampus. (C) 2015 Elsevier B.V. All rights reserved.