Effects of aging on neuroprotective and neurotoxic properties of microglia in neurodegenerative diseases

Abstract

The inflammatory process in the brain, which is accompanied by changes in the levels of proinflammatory cytokines and neurotrophins, along with the presence of activated microglia, has recently gained much attention in neurodegenerative diseases. Activated microglia produce either neuroprotective or neurotoxic factors. Many reports indicate that activated microglia promote degeneration of dopamine (DA) neurons in Parkinson's disease (PD). On the other hand, there are several lines of evidence that microglia also have a neuroprotective function. Microglia activated with lipopolysaccharide in the nigrostriatum of neonatal mice protect DA neurons against the PD-producing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), whereas activated microglia in aged mice promote DA cell death by MPTP. These results suggest that the function of activated microglia may change in vivo from neuroprotective to neurotoxic during aging as neurodegeneration progresses in the PD brain.