SWHR Emerging Scholars in Women’s Health Research Award  Symposium 2025

Nora is a sixth year PhD candidate in Michael Goard’s lab in the Molecular, Cellular, and Developmental Biology PhD program. She was born and raised in Buffalo, New York, where she fostered a love for science. In 2015 she moved to Washington, DC, where she received a BS in Cellular and Molecular Biology and a BA in Music Performance from the George Washington University. While in Washington, DC she initially studied the genetic underpinnings of body patterning in butterflies and later worked at the National Institutes of Health interrogating the neural circuitry of feeding behavior. Her current work focuses on investigating the neural circuits underlying sex differences in hippocampus. In pursuit of her thesis work she has developed technologies for longitudinal two-photon imaging in mice, as well as automated classification of murine hormonal state. She is currently supported by an NINDS F99 BRAIN Institute fellowship. While not in lab, Nora enjoys hiking, reading, and spotting new birds.

Abstract: Chronic Recording of Hippocampus across Pregnancy and Postpartum Reveals Long-term Structural Changes

Authors: Nora Wolcott [1], Lindsey Washiashi [1], Ariella Zulch [1], Emily Jacobs [1], Michael Goard [1].

[1] University of California, Santa Barbara

Pregnancy is a period of profound hormonal and physiological change that has been shown to cause widespread alterations in brain structure and function. Despite this, the underlying neuronal mechanisms driving these changes remain poorly understood. In particular, it is unclear how neuronal morphology contributes to pregnancy-related shifts in brain volume and to what extent these changes persist beyond parturition. To address this, we developed a novel noninvasive liquid chromatography-mass spectrometry (LC-MS) approach to quantify estradiol, progesterone, and corticosterone levels throughout pregnancy and postpartum in mice. We then performed longitudinal two-photon structural imaging using a custom-implanted glass microperiscope targeting the dorsal hippocampus. This approach enabled repeated measurements of dendritic spine density and branch morphology across several months. We observed an unprecedented 31% +/- 2% increase in spine density during pregnancy, followed by an 38% +/- 5% decline at parturition. Notably, 15 weeks postpartum spine density stabilized at 7% +/- 2% relative to baseline, a sustained increase from pre-pregnancy, suggesting long-term remodeling of hippocampal circuits. These structural changes were strongly correlated with circulating estradiol concentration, consistent with the well-established role of estrogen in hippocampal spinogenesis. In future work, we will use a miniaturized two-photon microscope to measure the functional activity of these neurons during foraging behavior across pregnancy and postpartum. Additionally, we will employ localized ERα and ERβ receptor knockdowns in the hippocampus to determine the extent to which estrogenic signaling mediates these structural and functional changes. Together, these findings are the first to longitudinally demonstrate that pregnancy induces lasting modifications to synaptic connectivity, a finding of major clinical relevance to the millions of women who experience pregnancy annually. Funding: This work was supported by the NSF (M.J.G., NeuroNex #1707287), the NIH (M.J.G., R01NS121919, N.S.W. F99NS139514), the Whitehall Foundation (M.J.G.), and the Larry Hillblom Foundation (M.J.G.).

Elizabeth is a fourth year PhD candidate at the University of California, Irvine School of Medicine in the Department of Pathology & Laboratory Medicine. Her work focuses on uncovering sex differences in Alzheimer’s disease through the lens of neuropathology, with a specific emphasis on people with Down syndrome. In addition to characterizing key proteins related to Alzheimer’s disease, she also examines the role of estrogen and its receptors in these pathways and how they may influence the presence of neuropathology. Seeking collaboration across disciplines, Elizabeth served as the Programs Chair for the Sex & Gender Differences Professional Interest Area through the Alzheimer’s Association and helps to organize their annual Great Debate. She was also recently selected as a UC President’s Pre-Professoriate Fellow, as part of the UC-Hispanic Serving Institutions Doctoral Diversity Initiative. Elizabeth is highly passionate about engaging the community outside of academia and participates in Buddy Walks with the Down Syndrome Association of Orange County. In addition, she helps to organize the annual Down Syndrome Showcase at UC Irvine, which highlights the performance and visual arts talents of the local community of people with Down syndrome. In her free time, she enjoys volunteering at the Shea Center for Equine Therapy, spending time with her dog, and practicing martial arts.

Abstract: Estrogen Receptor α Expression is Associated with Alzheimer’s Disease Pathology in People with Down Syndrome

Authors: Elizabeth J. Andrews [1], Freddy Gonzalez [1], Phong T. Ngo [1], Jordan Harp [2], Frederick Schmitt [2], Florence Lai [3], Elizabeth Head [1] and the ABC-DS Consortium.

[1] Department of Pathology & Laboratory Medicine, University of California Irvine, Irvine, CA

[2] Department of Neurology, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY

[3] Department of Neurology Massachusetts General Hospital, Harvard Medical School, Boston, MA

Down syndrome (DS) is associated with early Alzheimer disease (AD).  Women with DS show earlier age at menopause and lower bioavailable estrogen. We hypothesized women would have a higher degree of AD pathology at autopsy that would be associated with reduced estrogen receptor alpha (ERα) signaling. Immunohistochemistry for phosphorylated tau (p-tau; AT8), amyloid-β (Aβ; 6E10) and ERα, was performed using brain tissue from 156 individuals (frontal/occipital regions). Groups: DS (n=14/13, 1-39yr), DS with AD (DSAD) neuropathology (n=18/19, 42-61yr), late-onset AD (n=15/16, 72-96yr) and age-matched controls (n=50/47, 2-92yr). Western blotting of cytoplasmic and nuclear sub-cellular fractions was performed using frozen postmortem tissue (DSAD, 7M/7F). An association between Aβ and ERα (p<0.001) and a trend in association with p-tau (p=0.055) in the occipital cortex was observed in women with DS but not in men. Men with DSAD showed elevation in ERα protein in the nuclear and cytoplasmic fractions (p<0.05) compared to women with DSAD in both the occipital and frontal cortex. Women with DSAD may be losing neuroprotective signaling due to estrogen post-menopause, which could accelerate progression of AD pathology. It is critical to understand these differences for clinical trials and to investigate the potential benefit of hormone replacement therapy. Funding Acknowledgement: T32 AG000096, NIH/NIA U19AG068054, P50 AG16573, P30AG066519, BFF170008

Kathryn Bates is a third-year PhD candidate in the Integrative Neuroscience program at Dartmouth College in Hanover, New Hampshire. Kathryn earned her BS in Biology and Psychology from Longwood University in Farmville, Virginia, where she studied maternal behavior and its effects on cognition in rats across multiple generations. Kathryn’s dissertation research is centered on effective treatment to improve functional outcomes following traumatic brain injury. Using a mouse model of traumatic brain injury, her current project aims to characterize inflammatory and behavioral improvements following administration of a novel pharmacological agent. Her long-term goal is to evaluate clinically-relevant treatment using rodent models, and determine if sex is a mediator in the treatment response. When Kathryn isn’t in the lab you can find her baking, reading, or coaching adaptive sports!

Abstract: Traumatic Brain Injury in Women: Avenues for Novel Treatment

Authors: Kathryn Bates [1]

[1] Dartmouth College

Worldwide, traumatic brain injury (TBI) contributes to more death and disability than any other trauma-related injury. Although most TBIs are classified as mild to moderate in severity, brain injury can lead to sequelae, such as mood disorders, sleep disorders, and memory deficits, that can persist for weeks to years post-injury. Historically, sex differences in TBI have been understudied. Men have higher prevalence and mortality rates compared to women, which has been associated with increased high-risk behavior. However, women do not recover from TBI as well as their male counterparts. This talk will discuss recent literature surrounding TBI outcomes in women, focusing on injury prognosis and the potential for novel immunological treatments.