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Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine
Open accessAbstract
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.
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Shakesby, A. C., Anwyl, R., & Rowan, M. J. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-09-03638.2002 · Cited by 173
Molecular mechanisms of neuroplasticity and pharmacological implications: the example of tianeptine
McEwen, B. S., & Chattarji, S. (2004) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2004.09.008 · Cited by 174
Lee, T., Jarome, T., Li, S.-J., Kim, J. J., & Helmstetter, F. J. (2009) · NeuroReport · doi:10.1097/wnr.0b013e328332bb09 · Cited by 173
Increasing hippocampal neurogenesis: a novel mechanism for antidepressant drugs
Malberg, J., & Schechter, L. (2005) · Current Pharmaceutical Design · doi:10.2174/1381612053382223 · Cited by 167
Metadata
- Authors
- Czéh, B., Michaelis, T., Watanabe, T., Frahm, J., de Biurrun, G., van Kampen, M., Bartolomucci, A., & Fuchs, E.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2001-10-02
- Volume
- 98
- Issue
- 22
- Pages
- 12796-12801
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2093484024
- Cited by
- 1,091
- References
- 12
- FWCI
- 28.55
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.