[{"key":"dc.contributor.author","value":"Puri, Tanvi A.","language":""},{"key":"dc.date.accessioned","value":"2025-04-28T18:29:07Z","language":""},{"key":"dc.date.available","value":"2026-04-30T07:00:00Z","language":null},{"key":"dc.date.issued","value":"2025","language":"en"},{"key":"dc.identifier.uri","value":"http:\/\/hdl.handle.net\/2429\/90854","language":""},{"key":"dc.description.abstract","value":"Female-specific factors, such as pregnancy and menopause, influence brain health, but remain understudied in neuroscience. Females experience a disproportionately higher risk for neurodegenerative diseases such as Alzheimer\u2019s disease, and are often misdiagnosed or diagnosed late due to potentially distinct symptomology and treatment responses than males. Although recent guidelines and funding have brought greater attention to these factors, critical gaps in understanding how female-specific factors affect brain health remain. This thesis aims to address these gaps in the literature by investigating how previous reproductive history and estradiol (E2)-based menopausal hormone therapy (MHT) modulate brain structure, function, and cognitive outcomes. Chapter 2 investigated the effects of the age of menopause and E2 based MHT on various cognitive domains in middle aged females using human data from the Canadian Longitudinal Study on Aging. An earlier age of menopause was associated with impaired cognition across a variety of cognitive domains. Transdermal E2 was associated with higher episodic memory scores, whereas oral E2 was associated with higher prospective memory scores compared to no MHT, and E2 did not significantly affect executive function. Chapter 3 examined whether maternal age at first pregnancy and E2 differentially affected hippocampal neurogenesis, inflammation, and cognition in middle aged rodents. An older age of first pregnancy was associated with improved reversal learning and increased neurogenesis. E2 decreased anti-inflammatory cytokines based on the age of first pregnancy, indicating that E2 and the age of first pregnancy can interact to have long lasting effects on the aging brain. Chapter 4 investigated  the rapid effects of acute E2 on cell signaling cascades in hippocampal subregions of intact male and female rodents, as well as ovariectomized females. Acute E2 increased activation of the Akt and MAPK phosphoproteins in the CA1 region, and MAPK phosphoproteins in the dentate gyrus of OVX rats. Together, this work highlights the interactions between reproductive history and hormonal therapy to affect brain health and cognition, and demonstrates that female-specific factors modulate neuroplasticity and cognitive trajectories in middle age. This thesis underscores the importance of individualized approaches to women's health.","language":"en"},{"key":"dc.language.iso","value":"eng","language":"en"},{"key":"dc.publisher","value":"University of British Columbia","language":"en"},{"key":"dc.rights","value":"Attribution-NonCommercial-NoDerivatives 4.0 International","language":"*"},{"key":"dc.rights.uri","value":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/","language":"*"},{"key":"dc.title","value":"Past reproductive experience and estradiol affect brain health in middle-aged females","language":"en"},{"key":"dc.type","value":"Text","language":"en"},{"key":"dc.degree.name","value":"Doctor of Philosophy - PhD","language":"en"},{"key":"dc.degree.discipline","value":"Neuroscience","language":"en"},{"key":"dc.degree.grantor","value":"University of British Columbia","language":"en"},{"key":"dc.contributor.supervisor","value":"Galea, Liisa A. M.","language":""},{"key":"dc.contributor.supervisor","value":"Liu-Ambrose, Teresa","language":""},{"key":"dc.date.graduation","value":"2025-11","language":"en"},{"key":"dc.type.text","value":"Thesis\/Dissertation","language":"en"},{"key":"dc.description.affiliation","value":"Medicine, Faculty of","language":"en"},{"key":"dc.degree.campus","value":"UBCV","language":"en"},{"key":"dc.description.scholarlevel","value":"Graduate","language":"en"}]