title: Protective effects of resveratrol on the inhibition of hippocampal neurogenesis induced by ethanol during early postnatal life.
abstract: 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 Hes1 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.
authors: Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing 400038, China; The Battalion 5 of Cadet Brigade, Third Military Medical University, Chongqing 400038, China.
authors: Le
authors: L
authors: Xu
authors: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors: Yang
authors: Y
authors: Yang
authors: Southwest Eye Hospital, Southwest Hospital, Third Military Medical University, 400038, China.
authors: Lixiong
authors: L
authors: Gao
authors: Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing 400038, China.
authors: Jinghui
authors: J
authors: Zhao
authors: Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing 400038, China.
authors: Yulong
authors: Y
authors: Cai
authors: Department of Anesthesiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Jing
authors: J
authors: Huang
authors: Department of Anesthesiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Sheng
authors: S
authors: Jing
authors: Department of Anesthesiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Xiaohang
authors: X
authors: Bao
authors: Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing 400038, China.
authors: Ying
authors: Y
authors: Wang
authors: Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing 400038, China.
authors: Junwei
authors: J
authors: Gao
authors: Southwest Eye Hospital, Southwest Hospital, Third Military Medical University, 400038, China. Electronic address: haiweixu2001@163.com.
authors: Haiwei
authors: H
authors: Xu
authors: Department of Developmental Neuropsychology, School of Psychology, Third Military Medical University, Chongqing 400038, China. Electronic address: fanxiaotang2005@163.com.
authors: Xiaotang
authors: X
authors: Fan
mesh_terms: D000818:Animals; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055495:Neurogenesis; D018696:Neuroprotective Agents / Q000494:pharmacology*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000431:Ethanol; D048049:Extracellular Signal-Regulated MAP Kinases; D018398:Homeodomain Proteins; D018696:Neuroprotective Agents; D000077185:Resveratrol; D013267:Stilbenes; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse
keywords: Ethanol; Hippocampal development; Neural precursor cell; Neurogenesis; Resveratrol