title: Chronic desipramine prevents acute stress-induced reorganization of medial prefrontal cortex architecture by blocking glutamate vesicle accumulation and excitatory synapse increase.
abstract: BACKGROUND
  Although a clear negative influence of chronic exposure to stressful experiences has been repeatedly demonstrated, the outcome of acute stress on key brain regions has only just started to be elucidated. Although it has been proposed that acute stress may produce enhancement of brain plasticity and that antidepressants may prevent such changes, we still lack ultrastructural evidence that acute stress-induced changes in neurotransmitter physiology are coupled with structural synaptic modifications.
  
  
  METHODS
  Rats were pretreated chronically (14 days) with desipramine (10mg/kg) and then subjected to acute foot-shock stress. By means of serial section electron microscopy, the structural remodeling of medial prefrontal cortex glutamate synapses was assessed soon after acute stressor cessation and stress hormone levels were measured.
  
  
  RESULTS
  Foot-shock stress induced a remarkable increase in the number of docked vesicles and small excitatory synapses, partially and strongly prevented by desipramine pretreatment, respectively. Acute stress-induced corticosterone elevation was not affected by drug treatment.
  
  
  CONCLUSIONS
  Since desipramine pretreatment prevented the stress-induced structural plasticity but not the hormone level increase, we hypothesize that the preventing action of desipramine is located on pathways downstream of this process and/or other pathways. Moreover, because enhancement of glutamate system remodeling may contribute to overexcitation dysfunctions, this aspect could represent a crucial component in the pathophysiology of stress-related disorders.
authors.affiliation: Stereology and Electron Microscopy Laboratory, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University Hospital, Aarhus, Denmark (Drs Nava, Chen, and Nyengaard); Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark (Drs Nava, Treccani, Liebenberg, Chen, and Wegener); Pharmaceutical Research Center of Excellence, School of Pharmacy, North-West University, Potchefstroom, South Africa (Dr Wegener); 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 (Drs Treccani and Popoli). nicoletta.nava@ki.au.dk.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Nava
authors.affiliation: Stereology and Electron Microscopy Laboratory, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University Hospital, Aarhus, Denmark (Drs Nava, Chen, and Nyengaard); Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark (Drs Nava, Treccani, Liebenberg, Chen, and Wegener); Pharmaceutical Research Center of Excellence, School of Pharmacy, North-West University, Potchefstroom, South Africa (Dr Wegener); 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 (Drs Treccani and Popoli).
authors.forename: Giulia
authors.initials: G
authors.lastname: Treccani
authors.affiliation: Stereology and Electron Microscopy Laboratory, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University Hospital, Aarhus, Denmark (Drs Nava, Chen, and Nyengaard); Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark (Drs Nava, Treccani, Liebenberg, Chen, and Wegener); Pharmaceutical Research Center of Excellence, School of Pharmacy, North-West University, Potchefstroom, South Africa (Dr Wegener); 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 (Drs Treccani and Popoli).
authors.forename: Nico
authors.initials: N
authors.lastname: Liebenberg
authors.affiliation: Stereology and Electron Microscopy Laboratory, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University Hospital, Aarhus, Denmark (Drs Nava, Chen, and Nyengaard); Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark (Drs Nava, Treccani, Liebenberg, Chen, and Wegener); Pharmaceutical Research Center of Excellence, School of Pharmacy, North-West University, Potchefstroom, South Africa (Dr Wegener); 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 (Drs Treccani and Popoli).
authors.forename: Fenghua
authors.initials: F
authors.lastname: Chen
authors.affiliation: Stereology and Electron Microscopy Laboratory, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University Hospital, Aarhus, Denmark (Drs Nava, Chen, and Nyengaard); Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark (Drs Nava, Treccani, Liebenberg, Chen, and Wegener); Pharmaceutical Research Center of Excellence, School of Pharmacy, North-West University, Potchefstroom, South Africa (Dr Wegener); 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 (Drs Treccani and Popoli).
authors.forename: Maurizio
authors.initials: M
authors.lastname: Popoli
authors.affiliation: Stereology and Electron Microscopy Laboratory, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University Hospital, Aarhus, Denmark (Drs Nava, Chen, and Nyengaard); Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark (Drs Nava, Treccani, Liebenberg, Chen, and Wegener); Pharmaceutical Research Center of Excellence, School of Pharmacy, North-West University, Potchefstroom, South Africa (Dr Wegener); 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 (Drs Treccani and Popoli).
authors.forename: Gregers
authors.initials: G
authors.lastname: Wegener
authors.affiliation: Stereology and Electron Microscopy Laboratory, Centre for Stochastic Geometry and Advanced Bioimaging, Aarhus University Hospital, Aarhus, Denmark (Drs Nava, Chen, and Nyengaard); Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Risskov, Denmark (Drs Nava, Treccani, Liebenberg, Chen, and Wegener); Pharmaceutical Research Center of Excellence, School of Pharmacy, North-West University, Potchefstroom, South Africa (Dr Wegener); 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 (Drs Treccani and Popoli).
authors.forename: Jens Randel
authors.initials: JR
authors.lastname: Nyengaard
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D003345:Corticosterone / Q000097:blood; D003891:Desipramine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004597:Electroshock / Q000009:adverse effects; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D046529:Microscopy, Electron, Transmission; D008959:Models, Neurological; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000097:blood / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D013569:Synapses / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
chemical_list: D000929:Antidepressive Agents, Tricyclic; D050598:Vesicular Glutamate Transport Protein 1; D018698:Glutamic Acid; D003891:Desipramine; D003345:Corticosterone
keywords: desipramine; glutamate; stress; synapse