title: Impact of ketamine on learning and memory function, neuronal apoptosis and its potential association with miR-214 and PTEN in adolescent rats.
abstract: Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is used as a general pediatric anesthetic and anti-depressive drug. Recent studies suggest that ketamine enhances neuronal apoptosis in developing rats. The goal of this study is to explore whether ketamine could result in learning and memory impairment and neurodegeneration in adolescent rats, and if so, whether the effects of ketamine are associated with miR-214 and PTEN expression. Fifty-day-old SD rats were randomly divided into three groups receiving ketamine at 30, or 80 mg/kg, i.p. or saline for seven consecutive days. Twenty-four hours after the last treatment, learning and memory function were tested by the Morris water maze. The rats were then decapitated, and the brains were isolated for detection of neuronal apoptosis and protein PTEN expression by TUNEL and immunohistochemistry respectively. Expression levels of the miR-214 and PTEN in the hippocampus were measured by qRT-PCR and western blot analysis respectively. Ketamine administered to the adolescent rats at a dose of 80 mg/kg rather than the lower dose of 30 mg/kg caused learning and memory impairment, increased the number of apoptotic cells in the hippocampal CA1 region, cerebral cortex and subcortical region, decreased the miR-214 levels and increased PTEN protein expression in hippocampus. The results suggest that ketamine at a dose of 80 mg/kg in the adolescent rats is able to induce the learning and memory impairment and neurodegeneration, in which the down-regulation of miR-214 and high expression of PTEN protein may be involved.
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan Province, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan Province, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan Province, China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan Province, China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan Province, China.
authors.forename: Maohua
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Rush Medical College, Rush University, Chicago, Illinois, United Stated of America.
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan Province, China.
authors.forename: Shuzhi
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan Province, China.
authors.forename: Ni
authors.initials: N
authors.lastname: Tang
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D056547:CA1 Region, Hippocampal / Q000166:cytology; D002540:Cerebral Cortex / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory / Q000187:drug effects; D013550:Swimming
chemical_list: D035683:MicroRNAs; C559947:Mirn214 microRNA, rat; D007649:Ketamine; D051059:PTEN Phosphohydrolase