title: Pretreatment with minocycline restores neurogenesis in the subventricular zone and subgranular zone of the hippocampus after ketamine exposure in neonatal rats.
abstract: Ketamine is commonly used for anesthesia in pediatric patients. Recent studies indicated that ketamine exposure in the developing brain can induce neuroapoptosis and disturb normal neurogenesis, which will result in long-lasting cognitive impairment. Minocycline exerts neuroprotection against a wide range of toxic insults in neurodegenerative disease models. In the present study, we investigated whether the disturbed neurogenesis and behavioral deficits after ketamine neonatal exposure could be alleviated by minocycline. Postnatal day (PND)7 Sprague-Dawley rat pups randomly received either normal saline, ketamine, or minocycline 30min prior to ketamine administration, respectively. The rats were decapitated at PND14 for the detection of neurogenesis in the subventricular zone (SVZ) and subgranular zone (SGZ) of the hippocampus by immunostaining. The protein expression of p-Akt, p-GSK-3β in the SVZ and SGZ at 12h after anesthesia, PND10 and PND14 were assessed by western blotting analysis. At PND 42-47, spatial learning and memory abilities were measured by the Morris water maze in all groups. Our data showed that ketamine exposure in neonatal rats resulted in neurogenetic damage and persistent cognitive deficits, and that pretreatment with minocycline eliminated the brain development damage and improved the behavioral function in adult rats. Moreover, the protection of minocycline is associated with the PI3K/Akt signaling pathway.
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157(#)West 5 road, Xi'an, Shaanxi 710004, China; Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University, 76(#)Yanta West Road, Xi'an, Shaanxi 710061, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157(#)West 5 road, Xi'an, Shaanxi 710004, China; Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University, 76(#)Yanta West Road, Xi'an, Shaanxi 710061, China.
authors.forename: P K
authors.initials: PK
authors.lastname: Giri
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157(#)West 5 road, Xi'an, Shaanxi 710004, China; Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University, 76(#)Yanta West Road, Xi'an, Shaanxi 710061, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Lei
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157(#)West 5 road, Xi'an, Shaanxi 710004, China; Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University, 76(#)Yanta West Road, Xi'an, Shaanxi 710061, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157(#)West 5 road, Xi'an, Shaanxi 710004, China; Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University, 76(#)Yanta West Road, Xi'an, Shaanxi 710061, China.
authors.forename: Weisong
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157(#)West 5 road, Xi'an, Shaanxi 710004, China; Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University, 76(#)Yanta West Road, Xi'an, Shaanxi 710061, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University, 76(#)Yanta West Road, Xi'an, Shaanxi 710061, China.
authors.forename: Xinlin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University, 76(#)Yanta West Road, Xi'an, Shaanxi 710061, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, VA 22903, USA.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: Institute of Neurobiology, National Key Academic Subject of Physiology of Xi'an Jiaotong University, 76(#)Yanta West Road, Xi'an, Shaanxi 710061, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157(#)West 5 road, Xi'an, Shaanxi 710004, China. Electronic address: zhpbo@mail.xjtu.edu.cn.
authors.forename: Pengbo
authors.initials: P
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine; D053148:Caspase 3 / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D004334:Drug Administration Schedule; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects*; D020287:In Situ Nick-End Labeling; D007649:Ketamine / Q000633:toxicity*; D020547:Lateral Ventricles / Q000187:drug effects*; D018782:Maze Learning / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008911:Minocycline / Q000494:pharmacology*; D055495:Neurogenesis / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014404:Tubulin / Q000378:metabolism
chemical_list: D000089622:Doublecortin Domain Proteins; D018691:Excitatory Amino Acid Antagonists; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D014404:Tubulin; D007649:Ketamine; D053148:Caspase 3; D010751:Phosphopyruvate Hydratase; D008911:Minocycline; D001973:Bromodeoxyuridine
keywords: Akt; GSK-3β; brain development; ketamine; minocycline; neuroprotection