Antidepressant treatment with tianeptine reduces apoptosis in the hippocampal dentate gyrus and temporal cortex.
BACKGROUND
Recent clinical and preclinical studies suggest that major depression may be related to impairments of structural plasticity. Consequently, antidepressants may act by restoring altered rates of cell birth or death. Here, we investigated whether the antidepressant tianeptine would affect apoptosis in an animal model of depression, the psychosocially stressed tree shrew.


METHODS
Animals were subjected to a 7-day period of psychosocial stress before the onset of daily administration of tianeptine. Stress continued throughout the 28-day treatment period. In situ end labeling was used to detect apoptosis in hippocampus and adjacent temporal cortex.


RESULTS
Both stress and tianeptine treatment had a region-specific effect. Stress increased apoptosis in the temporal cortex, while it reduced it in the Ammons Horn. No significant effect was observed in the dentate gyrus. Interestingly, tianeptine treatment significantly reduced apoptosis in the temporal cortex and dentate gyrus, both in control and stressed animals, but had no effect in the Ammons Horn. Parallel Fluoro-Jade staining indicated that this apoptosis most likely represents non-neuronal cells.


CONCLUSIONS
This is the first report showing an anti-apoptotic effect of tianeptine in hippocampal subfields and temporal cortex. These findings are consistent with current theories that ascribe enhanced general cell survival to antidepressant action.
Lucassen
Paul J
PJ
Institute for Neurobiology, Faculty of Science, Swammerdam Institute for Life Sciences, University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam, The Netherlands.
Fuchs
Eberhard
E
Czéh
Boldizsár
B
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count / Q000379:methods; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects*; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D013266:Stilbamidines / Q000493:pharmacokinetics; D013315:Stress, Psychological / Q000188:drug therapy; D013702:Temporal Lobe / Q000166:cytology / Q000187:drug effects*; D013841:Thiazepines / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors; D014418:Tupaiidae
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D000929:Antidepressive Agents, Tricyclic; D005456:Fluorescent Dyes; D013266:Stilbamidines; D013841:Thiazepines; C050504:tianeptine