Sex differences and opposite effects of stress on dendritic spine density in the male versus female hippocampus

Dendritic spines are postsynaptic sites of excitatory input in the mammalia n nervous system. Despite much information about their structure, their fun ctional significance remains unknown. It has been reported that females in proestrus, when estrogen levels are elevated, have a greater density of api cal dendritic spines on pyramidal neurons in area CA1 of the hippocampus th an females in other stages of estrous (Woolley et al., 1990). Here we repli cate these findings and in addition, show that females in proestrus have a greater density of spines in area CA1 of the hippocampus than males. Moreov er, this sex difference in spine density is affected in opposite directions by stressful experience. In response to one acute stressful event of inter mittent tailshocks, spine density was enhanced in the male hippocampus but reduced in the female hippocampus. The decrease in the female was observed for those that were stressed during diestrus 2 and perfused 24 hr later dur ing proestrus. The opposing effects of stress were not evident immediately after the stressor but rather occurred within 24 hr and were evident on api cal and to a lesser extent on basal dendrites of pyramidal cells in area CA 1. Neither sex nor stress affected spine density on pyramidal neurons in so matosensory cortex. Sex differences in hippocampal spine density correlated with sex hormones, estradiol and testosterone, whereas stress effects on s pine density were not directly associated with differences in the stress ho rmones, glucocorticoids. In summary, males and females have different level s of dendritic spine density in the hippocampus under unstressed conditions , and their neuronal anatomy can respond in opposite directions to the same stressful event.