Aging and Sex Influence the Anatomy of the Rat Anterior Cingulate Cortex

Cognitive processes supported by the prefrontal cortex undergo an age-related decline. Until very recently, nonhuman animal models of aging have relied on the exclusive use of male subjects. This study was designed to investigate the influence of age, sex, and ovarian hormonal state on anatomy of the rat medial prefrontal cortex (anterior cingulate cortex). Dendritic tree extent and spine density were examined in young adult (3-5 mos.) and aged (20-24 mos.) male and female rats. Young adult females were examined either at proestrus or estrus, and aged females were examined in one of two reproductively senescent (estropausal) phases, persistent estrus or persistent diestrus. Neither the estrous cycle nor state of estropause influenced spine density or dendritic tree extent. However, the anatomy of the anterior cingulate cortex of young adult rats was sexually dimorphic, with males having greater dendritic spine density as well as arborization. While there was a reduction in density and tree extent with age for both sexes, this reduction was more pronounced for males, resulting in a disappearance of most sex differences with age. Thus the results of this study suggest that aging of the rodent cerebral cortex may follow a sexually dimorphic pattern.