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S-Ketamine Rapidly Reverses Synaptic and Vascular Deficits of Hippocampus in Genetic Animal Model of Depression.

التفاصيل البيبلوغرافية
العنوان: S-Ketamine Rapidly Reverses Synaptic and Vascular Deficits of Hippocampus in Genetic Animal Model of Depression.
المؤلفون: Ardalan M; Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University Hospital, Risskov, Denmark; Stereology and Electron Microscopy Laboratory, Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark; Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University, Aarhus, Denmark; Pharmaceutical Research Center of Excellence, School of Pharmacy (Pharmacology), North-West University, Potchefstroom, South Africa., Wegener G; Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University Hospital, Risskov, Denmark; Stereology and Electron Microscopy Laboratory, Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark; Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University, Aarhus, Denmark; Pharmaceutical Research Center of Excellence, School of Pharmacy (Pharmacology), North-West University, Potchefstroom, South Africa., Rafati AH; Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University Hospital, Risskov, Denmark; Stereology and Electron Microscopy Laboratory, Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark; Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University, Aarhus, Denmark; Pharmaceutical Research Center of Excellence, School of Pharmacy (Pharmacology), North-West University, Potchefstroom, South Africa., Nyengaard JR; Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University Hospital, Risskov, Denmark; Stereology and Electron Microscopy Laboratory, Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark; Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University, Aarhus, Denmark; Pharmaceutical Research Center of Excellence, School of Pharmacy (Pharmacology), North-West University, Potchefstroom, South Africa.
المصدر: The international journal of neuropsychopharmacology [Int J Neuropsychopharmacol] 2017 Mar 01; Vol. 20 (3), pp. 247-256.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 9815893 Publication Model: Print Cited Medium: Internet ISSN: 1469-5111 (Electronic) Linking ISSN: 14611457 NLM ISO Abbreviation: Int J Neuropsychopharmacol Subsets: MEDLINE
أسماء مطبوعة: Publication: 2015- : Oxford Oxford University Press
Original Publication: Cambridge, [England] : Cambridge University Press,
مواضيع طبية MeSH: Depression/*genetics , Hippocampus/*blood supply , Immobility Response, Tonic/*drug effects , Ketamine/*pharmacology , Microvessels/*drug effects , Neuronal Plasticity/*drug effects, Animals ; Disease Models, Animal ; Male ; Rats ; Rats, Inbred Strains ; Species Specificity ; Synapses/ultrastructure
مستخلص: Background: The neurovascular plasticity of hippocampus is an important theory underlying major depression. Ketamine as a novel glutamatergic antidepressant drug can induce a rapid antidepressant effect within hours. In a mechanistic proof of this concept, we examined whether ketamine leads to an increase in synaptogenesis and vascularization within 24 hours after a single injection in a genetic rat model of depression.
Methods: Flinders Sensitive Line and Flinders Resistant Line rats were given a single intraperitoneal injection of ketamine (15 mg/kg) or saline. One day later, their behavior was evaluated by a modified forced swim test. Microvessel length was evaluated with global spatial sampling and optical microscopy, whereas the number of asymmetric synapses was quantified through serial section electron microscopy by using physical disector method in the CA1.stratum radiatum area of hippocampus.
Results: The immobility time in the forced swim test among Flinders Sensitive Line rats with ketamine treatment was significantly lower compared with Flinders Sensitive Line rats without treatment. The number of nonperforated and perforated synapses was significantly higher in the Flinders Sensitive Line-ketamine vs the Flinders Sensitive Line-vehicle group; however, ketamine did not induce a significant increase in the number of shaft synapses. Additionally, total length of microvessels was significantly increased 1 day after ketamine treatment in Flinders Sensitive Line rats in the hippocampal subregions, including the CA1.stratum radiatum.
Conclusion: Our findings indicate that hippocampal vascularization and synaptogenesis is co-regulated rapidly after ketamine, and microvascular elongation may be a supportive factor for synaptic plasticity and neuronal activity. These findings go hand-in-hand with the behavioral observations, where ketamine acts as a potent antidepressant.
(© The Author 2016. Published by Oxford University Press on behalf of CINP.)
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فهرسة مساهمة: Keywords: antidepressant; hippocampus; ketamine; synaptic plasticity; vascularization
المشرفين على المادة: 690G0D6V8H (Ketamine)
تواريخ الأحداث: Date Created: 20161106 Date Completed: 20180521 Latest Revision: 20181113
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC5408982
DOI: 10.1093/ijnp/pyw098
PMID: 27815416
قاعدة البيانات: MEDLINE
الوصف
تدمد:1469-5111
DOI:10.1093/ijnp/pyw098