Biology subjects

Stark, S. M.

Publications and source records attributed to Stark, S. M..

4 recordsLinked to original sources

bioRxiv2025

ERb limits T cell-mediated inflammation to maintain immune homeostasis

Many autoimmune diseases exhibit a female sex bias in prevalence and severity, yet the mechanisms for this remain unclear. 17{beta}-estradiol, a steroid sex hormone with established immunomodulatory roles, signals through the nuclear receptors ER and ER{beta}, which are expressed by CD4+ T cells. Expression of ER{beta} is reduced in CD4+ T cells isolated from autoimmune disease patients, suggesting that dysregulated E2 signaling contributes to inflammation. We previously identified a novel role for ER{beta} in promoting the TGF{beta}-dependent differentiation of Foxp3+ Tregs, supporting the idea that ER{beta} has anti-inflammatory functions. In this study, we investigated the functional role of ER{beta} in effector T cells, which drive pathogenesis of many autoimmune diseases. We found that CD4+ T cells isolated from mice globally deficient in ER{beta} exhibit enhanced proliferation and Th1 polarization ex vivo, together with elevated levels of proinflammatory cytokines in response to T cell receptor (TCR) stimulation. We also found that transfer of ER{beta}-KO T cells to immunodeficient mice results in significantly worse inflammation in a murine model of colitis. Together, these findings suggest that T cell-specific ER{beta} functions as a brake on T cell-mediated inflammation, thereby helping to maintain immune homeostasis. HighlightsO_LICD4+ T cells express the nuclear estrogen receptor ER{beta} C_LIO_LIER{beta}-deficient T cells express higher levels of inflammatory cytokines and are hyperproliferative ex vivo C_LIO_LIDeletion of ER{beta} increases T cell-mediated inflammation in a murine model of colitis C_LI CRediT authorship contribution statementSKM: investigation, formal analysis, visualization, writing - original draft; AVB: investigation, formal analysis, visualization, writing - original draft and review and editing; SMS: investigation and formal analysis; CMS: investigation and formal analysis, ADK: investigation, MLR: investigation, WBT: investigation; WAG: conceptualization, funding acquisition, project administration, resources, supervision, formal analysis, visualization, writing-review and editing.

immunology↗

bioRxiv2019

Enriching hippocampal memory function in older adults through video games

Healthy aging is accompanied by a steady cognitive decline with clear losses in memory. Animal studies have consistently demonstrated that simply modifying an animals living environment (known as environmental enrichment) can have a positive influence on age-related cognitive decline in the hippocampus. Previously, we showed that playing immersive 3D video games can improve hippocampal-based memory in young healthy adults, suggesting that the exploration of the large open worlds of modern-day video games may act as proxy for environmental enrichment in humans. Here, we replicated our previous video game study in older adults and showing that playing video games for 4 weeks can improve hippocampal-based memory in a population that is already experiencing age-related decline in this memory. Furthermore, we showed that the improvements last for up to 4 weeks past the intervention, highlighting the potential of video games as intervention for age-related cognitive decline.

neuroscience↗

bioRxiv2019

Enriching hippocampal memory function in older adults through real-world exploration

Age-related structural and functional changes in the hippocampus can have a severe impact on hippocampally-dependent memory performance. Here we test the hypothesis that a real-world spatial exploration intervention will improve hippocampally-dependent memory performance in healthy older adults. We found that following our intervention, participants lure discrimination index (LDI) was significantly higher than it was at baseline, while traditional recognition scores remained relatively unchanged. These results point to the viability of a spatial exploration intervention for improving hippocampally-dependent memory in older adults.

neuroscience↗

bioRxiv2019

Age-related alterations in functional connectivity along the longitudinal axis of the hippocampus and its subfields

Aging causes hippocampal circuit alterations that differentially affect hippocampal subfields and are associated with age-related memory decline. Additionally, functional organization along the longitudinal axis of the hippocampus has revealed distinctions between anterior and posterior (A-P) connectivity. Here, we examined the functional connectivity (FC) differences between young and older adults at high-resolution within the medial temporal lobe network (entorhinal, perirhinal, and parahippocampal cortices), allowing us to explore how hippocampal subfield connectivity across the longitudinal axis of the hippocampus changes with age. Overall, we found reliably greater connectivity for younger adults than older adults between the hippocampus and PHC and PRC. This drop in functional connectivity was more pronounced in the anterior regions of the hippocampus than the posterior ones, consistent for each of the hippocampal subfields. Further, intra-hippocampal connectivity also reflected an age-related decrease in functional connectivity within the anterior hippocampus in older adults that was offset by an increase in posterior hippocampal functional connectivity. Interestingly, the anterior-posterior shift in older adults between hippocampus and PHC was predictive of lure discrimination performance on the MST, suggesting that this shift may reflect a compensation mechanism that preserves memory performance. While age-related dysfunction within the hippocampal subfields has been well-documented, these results suggest that the age-related A-P shift in hippocampal connectivity may also contribute significantly to memory decline in older adults.

neuroscience↗