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Sex differences and the effects of estrogen on cell proliferation, cell death and behaviour due to acute and repeated predator odour stress in adult rats Falconer, Erin Michelle


Possible sex differences in response to predator odour exposure were examined in adult rats. The first study measured behaviour, cell proliferation, and survival in the dentate gyrus of adult males and females in response to acute and repeated trimethyl thiazoline (TMT, the main component of fox feces) or control odour exposure. Rats were injected with one of the cell synthesis markers bromodeoxyuridine (BrdU) or [³H] thymidine and perfused 24 hours (cell proliferation) after an acute TMT exposure or after 5 days (cell survival) of repeated TMT exposure. After acute exposure, cell proliferation and death were suppressed in TMT-exposed males compared to control males, but not in females. Repeated TMT exposure in males increased cell death and increased the survival of new cells born on Day 1 of exposure. Males initially expressed more defensive behaviours in response to TMT but this expression habituated after repeated TMT exposure. This habituation was concurrent with enhanced new cell survival, possibly indicating that learning enhanced new cell survival. In a second study, we assessed whether ovarian hormones altered the response to acute TMT exposure in females. Ovariectomized (OVX) females were given either a high dose of estradiol (EB) or a low dose of estradiol and progesterone followed by a high dose of estradiol (EB-P). TMT exposure did not affect cell proliferation in any group. However, hormone treatment affected the behavioural, hormonal, and cell death response to TMT. EB increased cell proliferation and decreased defensive behaviour whereas EB-P decreased cell proliferation and increased defensive behaviour. Thus, we demonstrated that pre-treatment with a low dose of estradiol and progesterone profoundly affected the behavioural and cellular response to later administration of estradiol. Taken together, acute TMT exposure suppressed both cell proliferation and death while repeated TMT exposure enhanced new cell survival and cell death in males. However, female rats did not show a change in cell proliferation, regardless of hormone condition, but OVX female rats exhibited increased cell death in response to acute TMT exposure. This is the first demonstration of a sex difference in cell proliferation and cell death in the adult dentate gyrus in response to stress.

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