Destroying Existing Microglia is Necessary for Replacement Strategies to Work

Today's open access research is a demonstration in mice of approaches to replace near all microglia in the central nervous system. Microglia are innate immune cells of the brain, involved not just in destroying pathogens and errant cells, but also in ensuring the correct function of neural connections. With the progression of aging, their behavior shifts to become more harmful and inflammatory, and their numbers include ever more senescent cells. Senescent cells generate tissue dysfunction and chronic inflammation via the senescence-associated secretory phenotype, but beyond that microglia tend to adopt a more aggressive and inflammatory set of behaviors even when not senescent. This detrimental change is the consequence of some mix of persistent infection, protein aggregates, and other forms of the underlying molecular damage that drives aging. Microglial dysfunction contributes meaningfully to age-related neurodegeneration, as illustrated by the benefits produced in animal models by the selective destruction of senescent microglia. That approach has turned back the tau pathology characteristic of Alzheimer's disease in mice, for example. There is also evidence for inflammatory microglia to be involved in the progression of Parkinson's disease. More than just the senescent cells need to be replaced, or otherwise have their behavior changed for the better, however. Approaches involving clearance of a large fraction of microglia, and allowing them to regenerate t...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs