17-BETA-ESTRADIOL ENHANCES THE OUTGROWTH AND SURVIVAL OF NEOCORTICAL NEURONS IN CULTURE

Results of this investigation demonstrate that exposure to 17 beta-est radiol differentially and significantly regulates cortical nerve cell outgrowth depending on the cortical region. Parietal and occipital neu rons treated with 1 nM 17 beta-estradiol showed a greater magnitude of neuronal outgrowth whereas outgrowth of temporal cortex neurons was d ecreased in the presence of 1 nM 17 beta-estradiol. Frontal cortex neu rons showed a consistent enhancement of neuronal outgrowth that did no t reach statistical significance. The dose response profile for 17 bet a-estradiol regulation of the macromorphological features exhibited a bimodal dose response relationship whereas the dose response profile f or 17 beta-estradiol regulation of the micromorphological features exh ibited a dose response more characteristic of an inverted V-shaped fun ction. An antagonist to the NMDA receptor antagonist, AP5, abolished t he growth promoting effect of 17 beta-estradiol whereas the nuclear es trogen receptor antagonist ICI 182,780 did not. Lastly, neocortical ne urons exposed to 17 beta-estradiol exhibited greater viability and sur vival 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 effe cts of 17 beta-estradiol can be blocked by an antagonist to the NMDA g lutamate receptor and not by an antagonist to the estrogen nuclear rec eptor.