title: In vivo and in vitro ketamine exposure exhibits a dose-dependent induction of activity-dependent neuroprotective protein in rat neurons.
abstract: Anesthetic doses of ketamine induce apoptosis, as well as gene expression of activity-dependent neuroprotective protein (ADNP), a putative homeodomain transcription factor in rat pups (P7). This study investigated if ketamine induced ADNP protein in a dose-dependent manner in vitro and in vivo using primary cultures of cortical neurons and neonatal pups (P7). In vivo immunohistochemistry demonstrated a sub-anesthetic dose of ketamine increased ADNP in the somatosensory cortex (SCC) which was previously identified to be damaged by repeated exposure to anesthetic doses of ketamine. Administration of low-dose ketamine prior to full sedation prevented caspase-3 activation in the hippocampus and SCC. Primary cultures of cortical neurons treated with ketamine (10 μM-10mM) at 3 days-in vitro (3 DIV) displayed a concentration-dependent decrease in expanded growth cones. Furthermore, neuronal production and localization of ADNP varied as a function of both ketamine concentration and length of exposure. Taken together, these data support the model that ADNP induction may be partially responsible for the efficacy of a low-dose ketamine pre-treatment in preventing ketamine-induced neuronal cell death.
authors.affiliation: Neuroscience Program, Baldwin Wallace University, Berea, OH 44017, USA; Department of Chemistry, Baldwin Wallace University, Berea, OH 44017, USA.
authors.forename: B P
authors.initials: BP
authors.lastname: Brown
authors.affiliation: Neuroscience Program, Baldwin Wallace University, Berea, OH 44017, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Kang
authors.affiliation: Neuroscience Program, Baldwin Wallace University, Berea, OH 44017, USA; Department of Biology, Baldwin Wallace University, Berea, OH 44017, USA; Department of Chemistry, Baldwin Wallace University, Berea, OH 44017, USA.
authors.forename: K
authors.initials: K
authors.lastname: Gawelek
authors.affiliation: Neuroscience Program, Baldwin Wallace University, Berea, OH 44017, USA; Department of Psychology, Baldwin Wallace University, Berea, OH 44017, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Zacharias
authors.affiliation: Neuroscience Program, Baldwin Wallace University, Berea, OH 44017, USA; Department of Psychology, Baldwin Wallace University, Berea, OH 44017, USA; Department of Mathematics, Baldwin Wallace University, Berea, OH 44017, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Anderson
authors.affiliation: Neuroscience Program, Baldwin Wallace University, Berea, OH 44017, USA.
authors.forename: C P
authors.initials: CP
authors.lastname: Turner
authors.affiliation: Neuroscience Program, Baldwin Wallace University, Berea, OH 44017, USA; Department of Biology, Baldwin Wallace University, Berea, OH 44017, USA. Electronic address: jmorris@bw.edu.
authors.forename: J K
authors.initials: JK
authors.lastname: Morris
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D020439:Growth Cones / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D007150:Immunohistochemistry; D007649:Ketamine / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D013003:Somatosensory Cortex / Q000187:drug effects / Q000473:pathology / Q000502:physiology
chemical_list: C579795:ADNP protein, rat; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D007649:Ketamine; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: activity dependent protective protein; cortical neurons; growth cones; ketamine