Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine
Open Access
- 2 October 2001
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 98 (22), 12796-12801
- https://doi.org/10.1073/pnas.211427898
Abstract
Stress-induced structural remodeling in the adult hippocampus, involving debranching and shortening of dendrites and suppression of neurogenesis, provides a cellular basis for understanding the impairment of neural plasticity in the human hippocampus in depressive illness. Accordingly, reversal of structural remodeling may be a desirable goal for antidepressant therapy. The present study investigated the effect of tianeptine, a modified tricyclic antidepressant, in the chronic psychosocial stress model of adult male tree shrews (Tupaia belangeri), a model with high validity for research on the pathophysiology of major depression. Animals were subjected to a 7-day period of psychosocial stress to elicit stress-induced endocrine and central nervous alterations before the onset of daily oral administration of tianeptine (50 mg/kg). The psychosocial stress continued throughout the treatment period of 28 days. Brain metabolite concentrations were determined in vivo by proton magnetic resonance spectroscopy, cell proliferation in the dentate gyrus was quantified by using BrdUrd immunohistochemistry, and hippocampal volume was measured post mortem. Chronic psychosocial stress significantly decreased in vivo concentrations of N-acetyl-aspartate (−13%), creatine and phosphocreatine (−15%), and choline-containing compounds (−13%). The proliferation rate of the granule precursor cells in the dentate gyrus was reduced (−33%). These stress effects were prevented by the simultaneous administration of tianeptine yielding normal values. In stressed animals treated with tianeptine, hippocampal volume increased above the small decrease produced by stress alone. These findings provide a cellular and neurochemical basis for evaluating antidepressant treatments with regard to possible reversal of structural changes in brain that have been reported in depressive disorders.This publication has 62 references indexed in Scilit:
- The Corticosteroid Receptor Hypothesis of DepressionNeuropsychopharmacology, 2000
- Enhancement of Hippocampal Neurogenesis by LithiumJournal of Neurochemistry, 2000
- In vivo neurogenesis in the adult brain: regulation and functional implicationsEuropean Journal of Neuroscience, 2000
- STRESS AND HIPPOCAMPAL PLASTICITYAnnual Review of Neuroscience, 1999
- Psychosocial stress in tree shrews: Clomipramine counteracts behavioral and endocrine changesPharmacology Biochemistry and Behavior, 1996
- Estimation of metabolite concentrations from localized in vivo proton NMR spectraMagnetic Resonance in Medicine, 1993
- Multinuclear NMR Studies on the Energy Metabolism of Glial and Neuronal CellsDevelopmental Neuroscience, 1993
- BUdR as an S-phase marker for quantitative studies of cytokinetic behaviour in the murine cerebral ventricular zoneJournal of Neurocytology, 1992
- N-Acetyl-L-Aspartic acid: A literature review of a compound prominent in 1H-NMR spectroscopic studies of brainNeuroscience & Biobehavioral Reviews, 1989
- Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in ratsJournal of Comparative Neurology, 1965