Genetics variants that increase the activity of the C4 gene, which encodes part of the immune system's so-called "complement" cascade, have previously been shown to increase risk for schizophrenia in large genome-wide association studies. However, the mechanism through which such variants might contribute to the emergence of schizophrenia have not been clear because C4 has not previously been experimentally overexpressed.
During normal brain development, it's known that complement sticks to neuronal synapses and attracts microglia (immune cells in the brain), which engulf synaptic material in the process known as "synaptic pruning." When mis-regulated, this process can lead to abnormal connectivity in the brain.
Loss - Synapses - Cortex - Hallmark - Schizophrenia
Loss of synapses in the prefrontal cortex is a hallmark of schizophrenia, which led the authors to ask whether an overactive C4 gene might contribute to development of schizophrenia through mis-regulation of complement-mediated synaptic pruning by microglia. When they overexpressed complement C4 in the mouse prefrontal cortex, they found an increase in the level of microglial engulfment of...
Wake Up To Breaking News!