Estrogen deficiency results in apoptosis in the frontal cortex of adult female aromatase knockout mice

Abstract

The aromatase knockout (ArKO) mouse is completely estrogen deficient. We previously detected apoptosis in the hypothalamus of 1 year-old male ArKO mice. This study shows that 12 week-old female ArKO mice display spontaneous apoptosis of pyramidal neurons in the frontal cortex while wild-type (WT) littermates show no signs of apoptosis. Concomitantly, bcl-2 related anti-apoptotic genes are down-regulated whereas the pro-apoptotic gene TRADD is up-regulated in the female ArKO frontal cortex. This phenotype can be rescued by 3-week replacement of 17beta-estradiol. Furthermore, the apoptosis phenotype is exacerbated in 12-15 month-old female ArKO mice, which have 30% less neurons in the frontal ..