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Over Complement

Excess complement C4 – a gene well known in the immune system – affects neuron connections in a schizophrenia-like way

06 April 2020

Over Complement

Causing cognitive deficiencies and psychosis, schizophrenia is a serious mental disorder known to be highly heritable, yet its underlying causes are difficult to grasp. Among many genetic factors linked to this condition, the strongest association is with a gene involved in the immune system, known as complement C4. Scientists are closing in on how it contributes to schizophrenia, with recent evidence suggesting it triggers excessive pruning of connections between neurons (synapses) at adolescence, and now new work looking at the impact of excess C4 during development. Within the brain’s prefrontal cortex of mice (pictured, with cell nuclei in blue), extra C4 in pyramidal neurons (in green) encourages microglia (in magenta) to engulf and destroy more synapses, reducing neuronal connectivity, and leads to neurological defects and reduced social behaviours reminiscent of schizophrenia. Thinking about treatment, intervening while neural circuits are sensitive to the effects of C4 could represent an opportunity to reduce disease progression.

Written by Emmanuelle Briolat

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