Korean J Psychopharmacol.  2009 Nov;20(6):301-306.

Both R(-)- and S(+)-Citalopram Attenuate Neuronal Apoptosis in Murine Cortical Cell Culture

Affiliations
  • 1Research Institute for Neural Science and Technology, Ajou University School of Medicine, Suwon, Korea. jsnoh@ajou.ac.kr
  • 2Department of Psychiatry and Behavioral Sciences, Ajou University School of Medicine, Suwon, Korea.

Abstract


OBJECTIVE
Several lines of evidence have shown that neuronal injury might represent a possible pathway to mood disorders. The present study was performed to examine the possibility that the neuroprotective effects of R(-)- and S(+)-citalopram depend on types of neuronal cell death.
METHODS
Free radical neurotoxicity was induced in mixed cortical cell cultures by continuous exposure to 30 micrometer Fe++ for 24 hours, which produced hydroxyl radicals via a Fenton reaction. Cultures measuring excitotoxicity were exposed for 24 hours to 50 micrometer NMDA. Neuronal apoptosis was induced by 100 nM staurosporine exposure for 24 hours. Neuronal death was analyzed 24 hours later by measuring the efflux of lactate dehydrogenase (LDH) into the bathing medium or by counting viable neurons after staining with trypan blue.
RESULTS
Co-treatment with R(-)-or S(+)-citalopram prevented staurosporine-induced apoptosis of cultured cortical cells, as well as activation of caspase-3. In contrast to the differences between enantiomers found in serotonin uptake inhibition and in the in vivo behavioral depression model, both enantiomers in this study showed similar protective effects on staurosporine-induced apoptosis. Mixed cortical cell cultures exhibited marked swelling of the neuronal cell bodies accompanied by widespread neuronal death during the 24 hours following exposure to 30 micrometer Fe++ or 50 micrometer NMDA that was not sensitive to either the R(-)-or S(+)-enantiomers of citalopram.
CONCLUSION
These features suggest that the neuroprotective effect of citalopram depend on type of neuronal injury.

Keyword

Apoptosis; Antidepressant; Citalopram; Neuroprotection; Necrosis

MeSH Terms

Apoptosis
Baths
Caspase 3
Cell Culture Techniques
Cell Death
Citalopram
Depression
Diminazene
L-Lactate Dehydrogenase
Mood Disorders
N-Methylaspartate
Necrosis
Neurons
Neuroprotective Agents
Serotonin
Staurosporine
Trypan Blue
Caspase 3
Citalopram
Diminazene
L-Lactate Dehydrogenase
N-Methylaspartate
Neuroprotective Agents
Serotonin
Staurosporine
Trypan Blue
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