Sex differences in cell proliferation,cell death and defensive behavior following acute predator odor stress in adult rats

Males show suppressed cell proliferation in the hippocampus in response to acute stress but no studies to date have examined cell proliferation in response to acute stress in females. In the current study, we examined the effects of acute exposure to a predator odor stressor [trimethyl thiazoline (TMT); the main component of fox feces] or a control odor on cell proliferation and cell death in the dentate gyrus and on behavior in adult male and female [intact, ovariectomized (OVX) or OVX+estradiol benzoate (EB)] rats. Further, we examined whether TMT-induced changes in behavior were related to cellular changes. During TMT exposure, rats were injected with the cell synthesis marker bromodeoxyuridine and perfused 24 h later. Acute TMT exposure suppressed both cell proliferation and death in males but not in any group of females. Interestingly, in the OVX females we observed an increase in cell death that was eliminated by EB treatment. Consistent with prior studies, estradiol treatment increased cell proliferation regardless of odor condition. Regardless of sex or hormone treatment, TMT increased defensive behavior, suggesting that the behavioral response to TMT is dissociated from this cellular response. This is the first demonstration of a sex difference in cell proliferation and death in the adult dentate gyrus in response to stress.