title: Prenatal ketamine exposure causes abnormal development of prefrontal cortex in rat.
abstract: Ketamine is commonly used for anesthesia and as a recreational drug. In pregnant users, a potential neurotoxicity in offspring has been noted. Our previous work demonstrated that ketamine exposure of pregnant rats induces affective disorders and cognitive impairments in offspring. As the prefrontal cortex (PFC) is critically involved in emotional and cognitive processes, here we studied whether maternal ketamine exposure influences the development of the PFC in offspring. Pregnant rats on gestational day 14 were treated with ketamine at a sedative dose for 2 hrs, and pups were studied at postnatal day 0 (P0) or P30. We found that maternal ketamine exposure resulted in cell apoptosis and neuronal loss in fetal brain. Upon ketamine exposure in utero, PFC neurons at P30 showed more dendritic branching, while cultured neurons from P0 PFC extended shorter neurites than controls. In addition, maternal ketamine exposure postponed the switch of NR2B/2A expression, and perturbed pre- and postsynaptic protein expression in the PFC. These data suggest that prenatal ketamine exposure impairs neuronal development of the PFC, which may be associated with abnormal behavior in offsprings.
authors.affiliation: Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Tianyun
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Third Affiliated Hospital of Southern Medical University, Guangzhou, PR China.
authors.forename: Chuanxiang
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Anesthesiology, Third Affiliated Hospital of Southern Medical University, Guangzhou, PR China.
authors.forename: Haixing
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Anaesthetics, Pain Medicine &Intensive Care, Department of Surgery &Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK.
authors.forename: Daqing
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Xingrong
authors.initials: X
authors.lastname: Song
authors.affiliation: Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, PR China.|Co-innovation Center of Neuroregeneration, Nantong University, Jiangsu, PR China.
authors.forename: Libing
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000778:Anesthetics, Dissociative / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein / Q000096:biosynthesis / Q000235:genetics; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D005260:Female; D005865:Gestational Age; D006993:Hypnotics and Sedatives / Q000633:toxicity; D013287:Illicit Drugs / Q000633:toxicity; D007649:Ketamine / Q000633:toxicity*; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D017397:Prefrontal Cortex / Q000002:abnormalities* / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000235:genetics; D016708:Synaptophysin / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000778:Anesthetics, Dissociative; D000076122:Disks Large Homolog 4 Protein; D018691:Excitatory Amino Acid Antagonists; D006993:Hypnotics and Sedatives; D013287:Illicit Drugs; D007649:Ketamine; D016194:Receptors, N-Methyl-D-Aspartate; D016708:Synaptophysin; C501449:Dlg4 protein, rat; C121001:NR2B NMDA receptor; C569016:Syp protein, rat