Microglia phenotypes in aging-associated diseases

Zhuoran Yin

    Research output: ThesisThesis fully internal (DIV)

    1286 Downloads (Pure)

    Abstract

    Due to the improvement in the public health and medical care, the life span of human beings has elongated considerably over the last decades. Consequently, the occurrence of aging-associated diseases has also increased. Inflammation of the brain increases during aging and could be an important factor in neurodegenerative diseases. Microglia, the local immune cells in the brain, are the key cellular mediators of brain inflammation. The aim of this thesis is to explore changes of microglia in aging-associated neurodegenerative diseases. For this purpose, we studied microglia activity in animal models or human brain samples for aging, Alzheimer’s disease (AD), tauopathies, and obesity.
    Around the clumps of the protein amyloid beta that appear during AD, we observed very strong immune activity of brain immune cells. We found this in mouse models for AD as well as in the brains of deceased patients suffering from AD. We also observed increased inflammation in the white matter of brain tissue from deceased aged humans and from AD patients. Moreover, in animals fed with high-fat diet, we found an increased number of brain immune cells in the food satiety center of the brain. After application of a low-fat diet combined with limited food intake, we observed reduced inflammation in the white matter of the aging brain. Finally, a new transgenic tauopathy mouse model Tau 58/4 with deteriorating motor dysfunction is reported. These findings suggest microglia phenotypes in aging-associated diseases and provide the prognostic value for detecting the onset and progression of aging-associated diseases.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Boddeke, Erik, Supervisor
    • Eggen, Bart, Co-supervisor
    • De Deyn, Peter, Assessment committee
    • de Rooij, Sophia, Assessment committee
    • Bayer, T. A., Assessment committee, External person
    Award date13-Mar-2017
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-94-6182-773-9
    Electronic ISBNs978-94-6182-775-3
    Publication statusPublished - 2017

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