Multi-omic analysis in the hippocampus, serum, and CSF in response to inflammation, middle age and exercise

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dc.check.date2027-05-31
dc.contributor.advisorNolan, Yvonne M.
dc.contributor.advisorEnglish, Jane
dc.contributor.advisorLavelle, Aonghus
dc.contributor.authorAllard Dohm-Hansen, Sebastian
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2026-01-26T10:19:05Z
dc.date.available2026-01-26T10:19:05Z
dc.date.issued2025
dc.date.submitted2025
dc.description.abstractAs the global population ages, so too do our collective cognitive capacities. Brain ageing is rapidly becoming one of society’s most pressing health challenges. This includes both the natural decline of mental faculties but also pathological manifestations, like Alzheimer’s disease. Thus, tractable interventions that can delay brain ageing (such as physical exercise), and risk factors that might accelerate it (such as poor diet, gut dysbiosis, and neuroinflammation) are being researched at an accelerating rate. Over the last decade, a growing body of research has highlighted how all of these factors can exert their effects (positive and negative) on the brain via the systemic milieu (i.e. systemic circulation) and the gut-brain axis. Specifically, many mediators of the opposing effects of ageing and exercise on the brain and cognition are proteins and metabolites. This allows for the possibility of leveraging discovery -omics methods to identify the causal mediators and elucidate the molecular responses and pathways through which factors such as ageing, exercise, diet, inflammation, and gut dysbiosis affect the brain and systemic milieu. Here, we employ proteomics, metabolomics, transcriptomics, and a common data analysis pipeline to this very end. A particular focus is on middle age as a previously understudied life stage that presents a window of opportunity to shape future cognitive and brain ageing trajectories, and on exercise as a tractable intervention. We also cover models with relevance to ageing, including neuroinflammation, Alzheimer’s disease, diet, and gut dysbiosis. Another focus is on identifying molecular factors and pathways that impact adult hippocampal neurogenesis, the ongoing generation of new neurons within the dentate gyrus of the hippocampus. As a process known to be important to memory in humans and non-human animals, and one that steadily declines with age, along with its associated memory functions, it serves as a possible target of intervention to delay future brain and cognitive ageing. This thesis includes data from a wide range of studies (mainly animal models but also human data) that have recorded an equally diverse set of outcomes and readouts. However, the focus of this thesis is primarily on bioinformatics and the molecular mediators and pathways identified in these studies by the author. Accordingly, the results will mainly be discussed from the perspective of bioinformatics. Using this approach, we identify a novel exercise regulator of adult hippocampal neurogenesis that can be targeted to ameliorate its age-related decline in middle-aged rats. By integrating several datasets, we also identify molecular pathways in the hippocampus and serum on which middle age and voluntary exercise converge to exert opposing effects, which could possibly be harnessed to delay brain ageing. Yet, we also demonstrate how exercise can possible exacerbate underlying neuroinflammation. By analyzing a diverse set of matrices (tissues) with different - omics approaches, we identify benefits and challenges (both technical and biological) to their use in molecular studies of ageing, exercise, and relevant lifestyle and environmental factors. From a theoretical perspective, we argue that middle age is a unique period of life, associated with accelerating change in the brain and systemic milieu, with relevance to future cognitive ageing trajectories. From a methodological point of view, we highlight the utility of computational tools from the transcriptomics literature to address common problems in proteomics and metabolomics analyses, by leveraging common distributional and statistical properties across -omics modalities.en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationAllard Dohm-Hansen, D-J. H. S. 2025. Multi-omic analysis in the hippocampus, serum, and CSF in response to inflammation, middle age and exercise. PhD Thesis, University College Cork.
dc.identifier.endpage581
dc.identifier.urihttps://hdl.handle.net/10468/18462
dc.language.isoenen
dc.publisherUniversity College Corken
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/Frontiers for the Future::Awards/19/FFP/6820/IE/Mechanisms underpinning the interplay between chronic neuroinflammation and exercise on cognitive function during middle age/
dc.rights© 2025, Dee-Jay Heinrich Sebastian Allard Dohm-Hansen.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAging
dc.subjectExercise
dc.subjectBioinformatics
dc.subjectBrain
dc.subjectNeuroscience
dc.subjectAdult hipppocampal neurogenesis
dc.subjectInflammation
dc.subjectGut microbiome
dc.subjectSex differences
dc.subjectDiet
dc.subjectAlzheimer's disease
dc.titleMulti-omic analysis in the hippocampus, serum, and CSF in response to inflammation, middle age and exercise
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD - Doctor of Philosophyen
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