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Principal Investigator: BENEDETTA J LEUNER
Organization: OHIO STATE UNIVERSITY
Fiscal Year: 2024
Award: $192,059
Funding agency: Eunice Kennedy Shriver National Institute of Child Health and Human Development
PROJECT SUMMARY
Hormonal contraceptives (HC) are used by 10 million people in the United States alone. While HC have played
an important role in revolutionizing women’s health, the impact of HC on the brain have not been well studied,
especially during adolescence when HC use often begins. There is a critical need for this knowledge as a
growing number of recent studies suggest that use of HC, specifically among adolescents, is associated with
subsequent antidepressant use, greater likelihood of developing depression, and increased suicide risk.
Adolescence is a critical period of hormone-mediated brain development. Among the brain regions with the most
significant maturational changes during adolescence is the prefrontal cortex (PFC), or medial prefrontal cortex
(mPFC) in rodents. Because of the extended period of PFC/mPFC development and its well-known role in
depression, our central hypothesis is that adolescent exposure to contraceptive hormones may exacerbate the
risk for mood dysregulation by perturbing normal PFC development. We will employ daily administration of
hormones commonly used in HC (ethinyl estradiol and levonorgestrel) to adolescent rats and examine
interrelated endocrine, brain, and behavioral endpoints of relevance to the mPFC. Particular domains of interest
in these studies include central steroid hormone levels and receptor expression (Aim 1), synaptic pruning and
microglia-synaptic interactions (Aim 2), and long-term programming of behavioral outcomes dependent on
mPFC, including stress coping and cognitive flexibility (Aim 3). The research proposed in this application is
innovative because it investigates a widely used pharmaceutical for which there is little known about its effects
on the brain during an important time of the female lifespan when the potential to shape the trajectory of neural
development is high. The proposed research is significant because it is expected to generate knowledge about
the effects of adolescent HC use on the female PFC. Ultimately, neuroscientific studies on HC will advance
women’s health research and are a much needed step in achieving our long term goal of advancing knowledge
of how sex specific factors influence the brain across the lifespan.
Terms: <12-20 years old><21+ years old><Acne><Address><Adolescence><Adolescent><Adolescent Youth><Adrenal Cortex Hormones><Adult><Adult Human><Aeroseb-HC><Aquadiol><Behavior><Behavioral><Blood><Blood Reticuloendothelial System><Brain><Brain Nervous System><Brain region><Cell Body><Cells><Cetacort><Cognitive><Common Rat Strains><Contraceptive Agents><Contraceptive Usage><Contraceptives><Corpus Luteum Hormone><Cort-Dome><Cortef><Cortenema><Corticoids><Corticosteroids><Corticosterone><Cortisol><Cortispray><Cortril><DLG4><DLG4 gene><Data><Delta4-pregnene-3,20-dione><Dermacort><Development><Dimenformon><Diogyn><Diogynets><Dysmenorrhea><Eldecort><Elements><Encephalon><Endocrine><Endocrine Gland Secretion><Estrace><Estradiol><Estradiol-17 beta><Estradiol-17beta><Estraldine><Ethinyl Estradiol/Levonorgestr><Ethinyl Estradiol/Levonorgestrel><Exposure to><Feedback><Female><Female Adolescents><Female Health><Glucocorticoids><Goals><Gonadal Steroid Hormones><HPA axis><HPG axis><Hormonal><Hormones><Hortega cell><Human><Hydrocortisone><Hydrocortone><Hytone><Immune><Immunes><Impairment><Individual><Knowledge><Lead><Link><Major Depressive Disorder><Medial><Mediating><Menstrual Pain><Mental Depression><Microglia><Modern Man><Modification><Moods><Nerve Cells><Nerve Unit><Neural Cell><Neural Development><Neurocyte><Neuroendocrine><Neuroendocrine System><Neurons><Neurosecretory Systems><Nutracort><Ovarian hormone><Ovocyclin><Ovocylin><PSD95><Painful Menstruation><Pb element><Peripheral><Persons><Phagocytosis><Pharmaceutical Agent><Pharmaceuticals><Pharmacologic Substance><Pharmacological Substance><Play><Prefrontal Cortex><Pregn-4-ene-3,20-dione><Pregnenedione><Process><Proctocort><Progesterone><Progynon><Puberty><Rat><Rats Mammals><Rattus><Regulation><Reporting><Research><Risk><Rodent><Rodentia><Rodents Mammals><Role><SAP90><Sex Hormones><Sex Steroid Hormones><Shapes><Stress and Coping><Structure><Synapses><Synaptic><Teen><Teenagers><Testing><Therapeutic Estradiol><Therapeutic Hormone><Therapeutic Progesterone><Therapeutic Steroid Hormone><Time><United States><Woman><Women's Health><adolescence (12-20)><adolescent brain development><adolescent girl><adulthood><aged><analog><anti-depressant agent><anti-depressant drugs><anti-depressants><anti-depressive agents><behavior outcome><behavioral health><behavioral outcome><brain health><clinical depression><clinical effect><contraceptive use><coping with stress><critical developmental period><critical period><depression><developmental><experiment><experimental research><experimental study><experiments><female treatment><flexibility><flexible><gitter cell><gonadal steroids><heavy metal Pb><heavy metal lead><hormonal contraception><hormonal contraceptive><hypothalamic pituitary gonadal axis><hypothalamic-pituitary-adrenal (HPA) axis><hypothalamic-pituitary-adrenal axis><hypothalmus-pituitary-adrenal axis><innovate><innovation><innovative><interest><juvenile><juvenile human><life span><lifespan><major depression><major depression disorder><mesoglia><microglial cell><microgliocyte><neuroactive steroids><neurodevelopment><neuronal><neurosteroids><perivascular glial cell><pharmaceutical><receptor expression><response><sex><sex steroid><sexually active><social role><steroid hormone><steroid hormone receptor><stress-related coping><suicidal risk><suicide risk><synapse><synaptic pruning><teen years><teenage><treat females><treat women><treatment among females><treatment among women><treatment in females><treatment in women><women's treatment>