Previous studies have shown that the functional role of microglia in the cerebellum alters significantly as the brain ages. In this PhD thesis, we hypothesize that microglia are active participants in implementing cerebellar morphofunctional changes due to normal aging and may also contribute to the development of age-related pathologies. Furthermore, we hypothesize that some immunomodulators, such as melatonin, might effectively mitigate these deleterious microglia-mediated consequences. Our general approach is to study microglia participation under normal and pathological cerebellar physiological conditions. Microglia in young adults will be studied as a control, and these will be compared to microglia in healthy aged specimens, and to specimens under various neurodegenerative conditions. In addition, the immunomodulatory effects of melatonin on these processes will be examined. Cerebellar specimens for this study will be collected from 3- and 18-month-old male Wistar rats, and from genetically modified mice, such as APP/PS1; Cx3CR1-eGFP+/- mice (a model of Alzheimer’s disease). For analysis, we are applying a multidisciplinary set of methods, including immunohistochemistry, confocal microscopy, and Western blot. Preliminary data generated from this study will be presented.