[Frontiers in Bioscience 13, 3423-3438, May 1, 2008]

Microglial degeneration in the aging brain - bad news for neurons?

Wolfgang J. Streit, Kelly R. Miller, Kryslaine O. Lopes, Emalick Njie

Department of Neuroscience, University of Florida, Gainesville, FL 32610


1. Abstract
2. Introduction
3. Microglial activation
4. Microglial senescence
5. Iron accumulates in microglial cells with aging
5.1. Microglia and iron-induced oxidative stress
6. The self-renewal capacity of microglia in the aged brain
7. Mouse models of Alzheimer's disease
7.1. Extracellular trafficking and internalization of amyloid-beta
7.2. Lysosomal and non-lysosomal degradation of amyloid-beta
8. Consequences of amyloid-beta immunization and inflammation
9. Summary and Perspectives
7. Acknowledgements
11. References


We have long promulgated the idea that microglial cells serve an entirely beneficial role in the central nervous system (CNS), not only as immunological sentinels to fend off potentially dangerous infections, but also as constitutively neuroprotective glia that help sustain neuronal function in the normal and especially in the injured CNS when microglia become activated. In recent years, we have reported on the presence of degenerating microglial cells, which are prominent in the brains of aged humans and humans with neurodegenerative diseases, and this has led us to propose a hypothesis stating that loss of microglia and microglial neuroprotective functions could, at least in part, account for aging-related neurodegeneration. In the current review, we sum up the many aspects that characterize microglial activation and compare them to those that characterize microglial senescence and degeneration. We also consider the possible role of oxidative stress as a cause of microglial degeneration. We finish up by discussing the role microglial cells play in terms of amyloid clearance and degradation with the underlying idea that removal of amyloid constitutes a microglial neuroprotective function, which may become compromised during aging.