Synaptic Pruning and Schizophrenia – Role of Microglia and Future Directions
Synaptic pruning is an important developmental process that refines and optimises neuronal transmission.
In the healthy developing brain, this process is performed by the brain’s resident population of microglial cells. Microglia are commonly referred to as the immune cells of the CNS; however, they are dynamic and responsive cells that contribute to many physiological functions in the brain [Casano and Peri, 2015]:
- Microglia are primary innate immune cells that are phenotypically different and developmentally distinct from other macrophage populations in the periphery. Thus, they can be considered the ‘professional phagocytes’ in the central nervous system (CNS).
- Microglia also play a functional role in brain development, including the secretion of diffusible factors that stimulate synaptic formation, as well as phagocytosing of synaptic elements, axons, and dying cells.
- For example, in Alzheimer’s disease, microglia play a critical role in the uptake and proteolytic clearance of both soluble and fibrillary forms of β-amyloid.
- In addition to removing dying neurons, microglia might also actively promote neuronal cell death through a process known as “primary phagocytosis” or “phagoptosis.
- While microglia promote neuroprotection, TLR-induced activation of microglia and the release of pro-inflammatory molecules are responsible for neurotoxic processes in the course of various CNS diseases. Thus, the functional outcome of TLR-induced activation of microglia in the CNS depends on a subtle balance between protective and harmful effects. [Lehnardt, 2010]