The laboratory is focused on understanding how gonadal hormones, specifically estrogens, contribute to sex differences in fluid and energy homeostasis. Estrogens reduce water, salt, and food intakes and blood pressure in females but the exact mechanisms by which this occurs is unknown. Current research projects focus on (1) understanding how estrogen receptor subtypes mediate these behavioral changes, (2) identifying and exploring sex differences in thirst responses, and (3) investigating the role of aging on fluid and energy homeostasis in females.
Specific Research Projects:
THE ROLE OF ESTROGEN RECEPTOR SUBTYPES IN THE CONTROL OF FLUID AND FOOD INTAKE
The ovarian hormone estradiol (E2) decreases fluid and food intakes and recent work by the PI has identified the estrogen receptors (ER) responsible for mediating these behavioral changes. Current work in the laboratory focuses on understanding how these receptors mediate changes in fluid and food intake by identifying (1) key areas of the brain where these receptors act, (2) identifying intracellular signaling pathways affected by ER, (3) understanding the contributions of nuclear and membrane ER, and (4) identifying neuronal pathways that are targets for these E2 mediated effects.
SEX DIFFERENCES IN HYPOVOLEMIC AND OSMOTIC THIRST RESPONSES
Sex differences in thirst responses have been identified by are not well characterized. Current projects on this topic are designed to (1) further characterize the sex differences in both hypovolemic and osmotic thirst, (2) identify the role of body weight and blood pressure changes in mediating these sex differences, (3) identifying sex differences in the brain that may underlie the behavioral sex differences.
EFFECT OF AGING ON E2’S ANTI-DIPSOGENIC AND ANTI-NATRIOREXIGENIC EFFECTS
As females transition into "middle-age" they become less sensitive to the positive feedback from ovarian hormones. Previous work by the PI demonstrates that estradiol's anorexigenic effect is similar between young and middle-aged rats, but the estrogen sensitive genes involved in mediating food intake change during this time. Even less is known about the anti-dipsogenic and anti-natriorexigenic effects of estradiol in middle-aged animals. Current projects on this topic are designed to (1) determine whether water and saline intake and increases in blood pressure are differentially influenced by estradiol in young-adult and middle-aged rats and (2) determine if different brain areas and genes involved in fluid intake and blood pressure are differentially influenced by estradiol in young-adult and middle-aged rats.
EFFECTS OF DEHYDRATION ON COGNITIVE FUNCTION
It is well document that dehydration can impair multiple domains of cognitive function in humans. The mechanism, however, by which dehydration impairs cognition is unknown. Although animal models provide an excellent opportunity to investigate the mechanisms by which dehydration impairs cognitive function, there is very little research on this topic. Recent work by our group demonstrated that dehydration impaired performance in the novel object recognition (NOR) test in a sex and hormone-specific manner (Santollo, 2019). Ongoing research is further characterizing the effects of dehydration on cognitive performance and investigating the mechanisms by which dehydration impairs cognition.
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