17 beta-estradiol enhances the outgrowth and survival of neocortical neurons in culture

Results of this investigation demonstrate that exposure to 17 beta-estradiol differentially and significantly regulates cortical nerve cell outgrowth depending on the cortical region. Parietal and occipital neurons treated with 1 nM 17 beta-estradiol showed a greater magnitude of neuronal outgrowth whereas outgrowth of temporal cortex neurons was decreased in the presence of 1 nM 17 beta-estradiol. Frontal cortex neurons showed a consistent enhancement of neuronal outgrowth that did not reach statistical significance. The dose response profile for 17 beta-estradiol regulation of the macromorphological features exhibited a bimodal dose response relationship whereas the dose response profile for 17 beta-estradiol regulation of the micromorphological features exhibited a dose response more characteristic of an inverted V-shaped function. An antagonist to the NMDA receptor antagonist, AP5, abolished the growth promoting effect of 17 beta-estradiol whereas the nuclear estrogen receptor antagonist ICI 182,780 did not. Lastly, neocortical neurons exposed to 17 beta-estradiol exhibited greater viability and survival than control neurons over a two week period. These data indicate that 17 beta-estradiol can enhance the growth and viability of select populations of neocortical neurons and that the growth promoting effects of 17 beta-estradiol can be blocked by an antagonist to the NMDA glutamate receptor and not by an antagonist to the estrogen nuclear receptor.