Continuously delivered ovarian steroids do not alter dendritic spine density or morphology in macaque dorsolateral prefrontal cortical neurons

- Continuous estradiol does not alter spine density or morphology in macaque dlPFC.
- Adding cyclic progesterone to continuous estradiol does not affect dlPFC spines.
- dlPFC spine density returns to the baseline by 20 days post-estrogen injection.

Aged ovariectomized (OVX) female monkeys, a model for menopause in humans, show a decline in spine density in the dorsolateral prefrontal cortex (dlPFC) and diminished performance in cognitive tasks requiring this brain region. Previous studies in our laboratory have shown that long-term cyclic treatment with 17β-estradiol (E) produces an increase in spine density and in the proportion of thinner spines in layer III pyramidal neurons in the dlPFC of both young and aged OVX rhesus monkeys. Here we used 3D reconstruction of Lucifer yellow-loaded neurons to investigate whether clinically relevant schedules of hormone therapy would produce similar changes in prefrontal cortical neuronal morphology as long-term cyclic E treatment in young female monkeys. We found that continuously delivered E, with or without a cyclic progesterone treatment, did not alter spine density or morphology in the dlPFC of young adult OVX rhesus monkeys. We also found that the increased density of thinner spines evident in the dlPFC 24 h after E administration in the context of long-term cyclic E therapy is no longer detectable 20 days after E treatment. When compared with the results of our previously published investigations, our results suggest that cyclic fluctuations in serum E levels may cause corresponding fluctuations in the density of thin spines in the dlPFC. By contrast, continuous administration of E does not support sustained increases in thin spine density. Physiological fluctuations in E concentration may be necessary to maintain the morphological sensitivity of the dlPFC to E.