title: Neurovascular plasticity of the hippocampus one week after a single dose of ketamine in genetic rat model of depression.
abstract: Glutamatergic system and the structural plasticity hypothesis are principal components for rapid and sustained antidepressant effects of novel antidepressant therapeutics. This study represents the first investigation of the structural plasticity of the hippocampus as one of the main contributed mechanisms to the sustained anti-depressive effect of ketamine. Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL) rats were given a single intraperitoneal injection of ketamine (15 mg/kg) or saline 7 days before perfusion-fixed. The optical fractionator method was used to estimate the total number of neurons in the granular cell layer. Microvessel length in the molecular layer of DG was evaluated with global spatial sampling method. By use of the physical disector method, the number of synapses was estimated. The volume of the hippocampus was larger in the FRL-vehicle rats compared with FSL-vehicle group and in FSL-ketamine versus FSL-vehicle rats (P < 0.05). The number of non-perforated synapses was significantly higher in the FSL-ketamine versus FSL-vehicle group, (P = 0.01). A significant effect of ketamine on enhancement of the number of neurons in DG in FSL rats was observed (P = 0.01). The total length of the microvessels 1 week after ketamine treatment in the FSL rats significantly increased (P < 0.05). Our results indicate that neurovascular changes of hippocampus could be one of the possible mechanisms underlying the sustained antidepressant effect of ketamine by reversing alteration of the number of the excitatory synapses, neuronal number and length of the microvessels in the hippocampus. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Clinical Medicine, Translational Neuropsychiatry Unit, Aarhus University Hospital, Risskov, Denmark. Maryam.ardalan@clin.au.dk.|Department of Clinical Medicine, Stereology and Electron Microscopy Laboratory, Aarhus University Hospital, Aarhus, Denmark. Maryam.ardalan@clin.au.dk.
authors.forename: Maryam
authors.initials: M
authors.lastname: Ardalan
authors.affiliation: Department of Clinical Medicine, Translational Neuropsychiatry Unit, 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
authors.affiliation: Department of Clinical Medicine, Stereology and Electron Microscopy Laboratory, Aarhus University Hospital, Aarhus, Denmark.|Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Dipartimento Di Scienze Farmacologiche E Biomolecolari and Center of Excellence on Neurodegenerative Diseases, Università Degli Studi Di Milano, Milano, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Polsinelli
authors.affiliation: Aptinyx Inc, Evanston, Illinois.
authors.forename: Torsten M
authors.initials: TM
authors.lastname: Madsen
authors.affiliation: Department of Clinical Medicine, Stereology and Electron Microscopy Laboratory, Aarhus University Hospital, Aarhus, Denmark.|Centre for Stochastic Geometry and Advanced Bioimaging (CSGB), Aarhus University, Aarhus, Denmark.
authors.forename: Jens R
authors.initials: JR
authors.lastname: Nyengaard
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects*; D046353:Immobility Response, Tonic / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D055806:Microvessels / Q000187:drug effects* / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D007649:Ketamine
keywords: antidepressant; depression; flinders line; stereology; synaptic plasticity