title: Melatonin improves short and long-term neurobehavioral deficits and attenuates hippocampal impairments after hypoxia in neonatal mice.
abstract: Hypoxic encephalopathy is a common cause of neonatal seizures and long-term neurobehavioral abnormalities. The purpose of this study was to determine whether administration of melatonin, starting at 1h before hypoxia and then every 24 h for 3 days, influences short and long-term neurobehavioral development and hippocampal impairments in postnatal day 1 mice subjected to hypoxia (5% oxygen and 95% nitrogen for 120 min). Melatonin significantly attenuated hypoxia-induced neurobehavioral deficits, including sensorimotor performance, locomotor functions, and hyperactivity up to two weeks after hypoxia insult. The above-mentioned functional benefits of melatonin were associated with attenuation of cell death in the hippocampus. Importantly, melatonin improved learning and memory performance in the Morris water test, as associated with significantly increased proliferating cells (BrdU-positive cells) and differentiating neuroblasts (doublecortin-positive neuroblasts) in the hippocampus of hypoxic animals at 30 days after hypoxia. In addition, melatonin significantly decreased microglial activation and overproduction of pro-inflammatory mediators (tumor necrosis factor-α, interleukin-1β and nitric oxide) from 3 to 30 days after hypoxia, possibly by inhibiting NF-κB activation in the hippocampus. The present results show that melatonin has short- and long-term protective effects against hypoxia-induced neurobehavioral deficits in the neonatal mouse. These beneficial effects are associated with increasing neurogenesis and attenuation of cell death and inflammatory responses in the hippocampus.
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Dexiang
authors.initials: D
authors.lastname: Liu
authors.forename: Jingmin
authors.initials: J
authors.lastname: Zhan
authors.forename: Kai
authors.initials: K
authors.lastname: Xie
authors.forename: Xueer
authors.initials: X
authors.lastname: Wang
authors.forename: Xiuying
authors.initials: X
authors.lastname: Xian
authors.forename: Jianhua
authors.initials: J
authors.lastname: Gu
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Chen
authors.forename: Aijun
authors.initials: A
authors.lastname: Hao
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002534:Hypoxia, Brain / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D053583:Interleukin-1beta / Q000235:genetics; D018782:Maze Learning / Q000187:drug effects; D008550:Melatonin / Q000627:therapeutic use*; D008568:Memory / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D002492:Central Nervous System Depressants; D053583:Interleukin-1beta; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; D008550:Melatonin
keywords: Hippocampus; Hypoxia; Melatonin; Neurobehavioral deficits