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.
Role of microglia in disease
A causal role for microglia in the pathogenesis of neuropathic pain has been demonstrated through P2X receptor. P2X receptors are upregulated following injury and the increase in purinergic signaling activates p38-mitogen-activated protein kinase (p38 MAPK). The increase in p38 MAPK signaling leads to greater microglial release of brain-derived neurotrophic factor (BDNF). BDNF released from microglia induces neuronal hyperexcitability through interaction with the TrkB receptor.