Testosterone modulation of dendritic spines of somatosensory cortical pyramidal neurons

Abstract

Brain structures and functions are increasingly recognized to be directly affected by gonadal hormones, which classically determine reproductive functions and sexual phenotypes. In this regard, we found recently that ovariectomy trimmed the dendritic spines of female rat primary somatosensory cortical neurons and estradiol supplement reversed it. Here, we investigated whether in the male androgen also has a cortical modulatory effect. The dendritic arbors and spines of rat somatosensory cortical pyramidal neurons were studied following intracellular dye injection and three-dimensional reconstruction. Dendritic spines, but not length, of the layers III and V pyramidal neurons were found reduced at 2 weeks and rebounded slightly at 4 weeks and further at 8 and 24 weeks following castration, which, however, remained significantly fewer than those of the intact animals. Two weeks of osmotic pump-delivered testosterone treatment to animals castrated for 4 weeks replenished serum testosterone and reversed the densities of dendritic spines on these neurons to control animal levels. Androgen receptor appears to mediate this effect as its antagonist flutamide reduced the dendritic spines of normal adult rats while causing a mild feedback surge of serum testosterone. On the other hand, blocking the conversion of testosterone to estrogen with the aromatase inhibitor anastrozole failed to alter the dendritic spine densities in male adult rats. In conclusion, these results support our hypothesis that testosterone acts directly on the androgen receptor in males to modulate the dendritic spines of somatosensory cortical output neurons.