title: S(+)-ketamine up-regulates neuronal regeneration associated proteins following glutamate injury in cultured rat hippocampal neurons.
abstract: In previous studies, racemic ketamine improved neurological outcome after experimental brain injury and S(+)-ketamine demonstrated neuroprotective effects in neurons after damage in vitro. We compared the expression of regeneration-associated proteins in rat hippocampal neurons after glutamate injury and treatment with S(+)-ketamine versus racemic ketamine. Following an 8 minute exposure to 100 microM glutamate, neurons were maintained untreated or in the presence of S(+)-ketamine or racemic ketamine (10(-4) M, 10(-5) M, 10(-6) M) for one week. Growth-associated protein-43 (GAP-43) and synaptosomal-associated protein-25 (SNAP-25) was analyzed by Western Blotting, the mitochondrial transmembrane potential (MTP) by fluorescence imaging, and [3H]2-deoxy-D-glucose ([3H]2-DG) uptake by scintillation spectrometry. Seven days after exposure, GAP-43 decreased to 15% and SNAP-25 to 30% in the glutamate-injured, untreated neurons. The MTP declined to 50% and [3H]2-DG to 30%. Both S(+)-ketamine and racemic ketamine at 10(-4) M and 10(-5) M minimized the decline in MTP, almost maintaining it at control value. Additionally, S(+)-ketamine and racemic ketamine decreased the reduction in [3H]2-DG. S(+)-ketamine at 10(-4) M and 10(-5) M and racemic ketamine at 10(-4) M reduced the decline in SNAP-25 to 60% of controls (P < .05). However, S(+)-ketamine at 10(-4) M and 10(-5) M only reversed the decrease in GAP-43 to 50% and 40% of controls, respectively (P < .05). We conclude that the synthesis of a growth-associated protein related to plasticity and repair in the adult nervous system is increased by S(+)-ketamine but is not increased by racemic ketamine.
authors.affiliation: Institut für Anaesthesiologie, Technische Universität München, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Himmelseher
authors.forename: E
authors.initials: E
authors.lastname: Pfenninger
authors.forename: E
authors.initials: E
authors.lastname: Kochs
authors.forename: M
authors.initials: M
authors.lastname: Auchter
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D019922:GAP-43 Protein / Q000032:analysis; D018698:Glutamic Acid / Q000633:toxicity*; D006624:Hippocampus / Q000166:cytology* / Q000502:physiology*; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D007649:Ketamine / Q000494:pharmacology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008565:Membrane Proteins; D008928:Mitochondria / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D050825:Synaptosomal-Associated Protein 25; D013997:Time Factors
chemical_list: D019922:GAP-43 Protein; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D018698:Glutamic Acid; D007649:Ketamine