Complement-Mediated Synaptic Pruning During Development

Synaptic pruning is a developmental process where a large number of synaptic connections are selectively eliminated to increase the efficiency of synaptic transmission. This process involves elimination of week synapses to allow the maintenance and strengthening of stronger synapses that have developed proper synaptic connections.

The complement system (CS) has emerged as a candidate mechanism where complement proteins C1q and C3 localize to and mediate the pruning of immature synapses. These CS components were shown to act as signaling molecules that lead to the engulfment of unwanted synapses by microglia and their elimination. This mechanism is thought to involve an unknown factor (x) secreted by astrocytes that induces the production of C1q by neurons. Neuron and microglia-derived C1q initiates the complement cascade where complement component C3 is activated and deposited on synapses. Phagocytosis of complement-tagged synapses is then mediated through interactions between complement proteins and their receptors [complement receptor (CR)] on microglia.

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