The involvement of microglia and alpha-synuclein had been studied in relation to the dopaminergic cell loss in the substantia nigra and the motor symptoms. So far, however, little attention was paid to such changes in extra-nigral regions, involved in non-motor symptoms. Microglia further form a diverse cell group with specific phenotypes, that can exert either beneficial or detrimental effects, depending on their location and context. Hence, the overall aim of this thesis was to study microglia in brain regions that are differently affected during PD, and to study whether or not such differences relate to the alpha-synuclein neuropathology.
We show that microglia respond to the alpha-synuclein neuropathology in a highly brain-region specific manner, a response that is particularly prominent during the early stages of PD. More insight into the mechanisms driving these microglial responses will contribute to a better understanding of the etiology of, and possible ways to prevent, PD-related pathology and symptomatology.
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