The impacts of stress, exercise, and extracellular vesicles on the brain
Connolly, Meghan Grace
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https://hdl.handle.net/2142/130001
Description
Title
The impacts of stress, exercise, and extracellular vesicles on the brain
Author(s)
Connolly, Meghan Grace
Issue Date
2025-05-23
Director of Research (if dissertation) or Advisor (if thesis)
Rhodes, Justin S
Doctoral Committee Chair(s)
Rhodes, Justin S
Committee Member(s)
Raetzman, Lori T
Mahoney, Megan M
Gritton, Howard J
Department of Study
Neuroscience Program
Discipline
Neuroscience
Degree Granting Institution
University of Illinois Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Stress
Exercise
Extracellular vesicles
Neurogenesis
Microglia
Hippocampus
Striatum
Abstract
Stress and exercise are major regulators of brain plasticity, influencing neuroinflammation, motivation, and neurogenesis through central and peripheral mechanisms. Stress activates neuroimmune signaling pathways that disrupt brain homeostasis, while exercise promotes resilience by enhancing adaptive neural plasticity. Both circulating extracellular vesicles (EVs), and microglial activation states have emerged as important mediators of these effects, yet their roles in brain adaptation to stress and exercise remain incompletely understood. This dissertation investigates how stress, exercise, and exercise-derived EVs influence neuroplasticity and neuroimmune function in the hippocampus and striatum. Chapter 1 reviews the effects of stress and exercise on the brain, with a focus on microglial activation, neurogenesis, and extracellular vesicle signaling. Chapter 2 reports that plasma-derived EVs from exercising mice enhance adult hippocampal neurogenesis and astrogliogenesis. Chapter 3 examines whether human-derived ExerVs mitigate the adverse effects of simulated microgravity stress, revealing no significant changes in neuroinflammation, microglial proliferation, or neurogenesis. Chapter 4 uses single-nucleus RNA sequencing to characterize microglial transcriptional responses in the striatum, showing that stress and exercise each induce distinct, non-overlapping activation states. Chapter 5 synthesizes these findings and discusses how peripheral signals and microglial plasticity shape brain resilience and vulnerability. Together, these findings provide new insight into the molecular and cellular mechanisms through which systemic and immune-mediated processes regulate brain plasticity and identify potential targets for promoting cognitive resilience and mitigating stress-related neuroinflammatory dysfunction.
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