title: Rapid antidepressant effect of ketamine correlates with astroglial plasticity in the hippocampus.
abstract: Astroglia contribute to the pathophysiology of major depression and antidepressant drugs act by modulating synaptic plasticity; therefore, the present study investigated whether the fast antidepressant action of ketamine is reflected in a rapid alteration of the astrocytes' morphology in a genetic animal model of depression.
  
  
  
  S-Ketamine (15 mg·kg-1) or saline was administered as a single injection to Flinders Line (FSL/ FRL) rats. Twenty-four hours after the treatment, perfusion fixation was carried out and the morphology of glial fibrillary acid protein (GFAP)-positive astrocytes in the CA1 stratum radiatum (CA1.SR) and the molecular layer of the dentate gyrus (GCL) of the hippocampus was investigated by applying stereological techniques and analysis with Imaris software. The depressive-like behaviour of animals was also evaluated using forced swim test.
  
  
  
  FSL rats treated with ketamine exhibited a significant reduction in immobility time in comparison with the FSL-vehicle group. The volumes of the hippocampal CA1.SR and GCL regions were significantly increased 1 day after ketamine treatment in the FSL rats. The size of astrocytes in the ketamine-treated FSL rats was larger than those in the FSL-vehicle group. Additionally, the number and length of the astrocytic processes in the CA1.SR region were significantly increased 1 day following ketamine treatment.
  
  
  
  Our results support the hypothesis that astroglial atrophy contributes to the pathophysiology of depression and a morphological modification of astrocytes could be one mechanism by which ketamine rapidly improves depressive behaviour.
authors.affiliation: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University Hospital, Risskov, Denmark.
authors.forename: Maryam
authors.initials: M
authors.lastname: Ardalan
authors.affiliation: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University Hospital, Risskov, Denmark.|Center for Stochastic Geometry and Advanced Bioimaging, Aarhus University, Aarhus, Denmark.
authors.forename: Ali H
authors.initials: AH
authors.lastname: Rafati
authors.affiliation: Stereology and Electron Microscopy Laboratory, Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.|Center for Stochastic Geometry and Advanced Bioimaging, Aarhus University, Aarhus, Denmark.
authors.forename: Jens R
authors.initials: JR
authors.lastname: Nyengaard
authors.affiliation: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University Hospital, Risskov, Denmark.|Pharmaceutical Research Center of Excellence, School of Pharmacy (Pharmacology), North-West University, Potchefstroom, South Africa.
authors.forename: Gregers
authors.initials: G
authors.lastname: Wegener
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects*; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000928:Antidepressive Agents; D007649:Ketamine