Stimulation of 5-HT1A receptor inhibits apoptosis induced by serum deprivation in cultured neurons from chick embryo.

Primary cultures of neurons from chick embryo telencephalons were deprived of serum to induce apoptotic cell death. After 24 h of serum withdrawal, we found a reduction in cell viability from 85% to 72% and an increase in the number of apoptotic cells from 12% to 29%. The 5-HT1A receptor agonist 8-OH-DPAT inhibited the decrease in cell viability and reduced the number of apoptotic cells in a concentration-dependent manner. The anti-apoptotic effect of 8-OH-DPAT (1 microM) could be blocked by adding the selective 5-HT1A antagonist MPPI (10 microM), but not in the presence of the dopamine receptor antagonist chlorpromazine (1 microM) and of the beta-receptor blocker propranolol (10 microM). In addition, anti-nerve growth factor (NGF) antibodies inhibited the protective effect of 8-OH-DPAT, suggesting that induction of NGF was involved in the mechanism of action. Serum deprivation alone already induced a release of NGF (10 pg/flask) which protected the neurons from further cell death. Accordingly, the addition of the same amount of exogenous NGF restored cell viability up to control level and addition of anti-NGF antibodies further decreased cell viability to 56%. In the presence of 8-OH-DPAT (1 microM), the level of NGF in the culture medium was only slightly yet consistently increased compared to serum deprivation from 4 h onwards. Thus, our data suggest that the anti-apoptotic effect of 8-OH-DPAT is mediated by the stimulation of 5-HT1A receptors. Furthermore, the induction of neuronal NGF synthesis and secretion contributes to its neuroprotective action.