Serotonin promotes the survival of cortical glutamatergic neurons in vitro.
The appearance of 5-hydroxytryptamine (serotonin; 5-HT) in the cerebral cortex coincides with developmental events such as cell proliferation, survival, and differentiation. We tested the hypothesis that 5-HT plays a role in these events by examining rat cortical progenitor cells in vitro. Using bromodeoxyuridine incorporation we found that 5-HT did not affect the proliferation of these cells, but a cell survival assay indicated that it promoted their survival. The observed survival effect was mimicked by the 5-HT2a/2c receptor agonist alpha-methyl-5-HT and blocked by the 5-HT2a receptor antagonist cinanserin. Consistent with increased survival was the finding, using the terminal transferase nick end labeling method, of reduced cell death in cultures exposed to 5-HT. Immunohistochemical analysis with cell-specific markers revealed that the effect of 5-HT was directed specifically to the glutamate-containing neuronal population and not to any other cortical cell types. These results indicate that 5-HT does not exert its effects on dividing neuroepithelial cells in the developing cortex, but rather on postmitotic neurons.
Dooley
A E
AE
Department of Anatomy and Developmental Biology, University College London, United Kingdom.
Pappas
I S
IS
Parnavelas
J G
JG
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology; D002928:Cinanserin / Q000494:pharmacology; D018698:Glutamic Acid / Q000032:analysis*; D009474:Neurons / Q000737:chemistry / Q000145:classification / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology*
D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; C042390:alpha-methylserotonin; D012701:Serotonin; D018698:Glutamic Acid; D002928:Cinanserin