Microglia
Research has discovered dystrophic (defective development) human microglia. "These cells are characterized by abnormalities in their cytoplasmic structure, such as deramified, atrophic, fragmented or unusually tortuous processes, frequently bearing spheroidal or bulbous swellings." The incidence of dystrophic microglia increases with aging. Microglial degeneration and death have been reported in research on Prion disease, Schizophrenia and Alzheimer's disease, indicating that microglial deterioration might be involved in neurodegenerative diseases. A complication of this theory is the fact that it is difficult to distinguish between "activated" and "dystrophic" microglia in the human brain.
Radiation-induced cognitive decline
Radiation therapy usually results in chronic inflammation, and in the brain this inflammatory response comes in the form of activated microglia cells. Once activated, these microglia cells start to release stress hormones and various pro-inflammatory cytokines. Some of what is released by the activated microglia cells, like the glucocorticoid stress hormone, may result in a decrease in neurogenesis. To investigate this concept, an animal study was performed by Monje et al. in order to determine the specific cytokines or stress hormones that were released by activated microglial cells that decrease neurogenesis in an irradiated hippocampus. In this study, microglia cells were exposed to bacterial lipopolysaccharide to elicit an inflammatory response, thus activating the microglia cells. These activated microglia were then co-cultured with normal hippocampal neural stem cells. Also, as a control, non-activated microglia cells were co-cultured with normal hippocampal neural stem cells. In comparing the two co-cultures, it was determined that neurogenesis in the activated microglia cell culture was 50% less than in the control. A second study was also performed to ensure that the decrease in neurogenesis was the result of released cytokines and not cell-to-cell contact of microglia and stem cells. In this study, neural stem cells were cultured on preconditioned media from activated microglia cells and a comparison was made with a neural stem cells cultured on plain media. The results of this study indicated that neurogenesis also showed a similar decrease in the preconditioned media culture versus the control.