L5

Question 1

What are complement proteins?

Answer 1

Part of immune system and play important role in targeting foreign antigens for destruction

Question 2

Discuss the association between complement and schizophrenia. Propose a possible mechanism that could explain the role of C4 in schizophrenia

Answer 2

1. Recent work has associated complement component 4 (C4) with SZ
2. Studies with immunofluorescence showed that C4 protein localizes to neuronal SYNAPSES and DENDRITES in human cultured neurons
3. C4 protein has shown to be elevated in brains of individuals with SZ compared to non-SZ brains

Question 3

Propose a possible mechanism that could explain the role of C4 in schizophrenia

Answer 3

• In mice, C4 mediates synaptic elimination during post-natal development. C4 is expressed at synapses between RGC projections to the LGN during synaptic pruning
  In the immune system, C4 promotes activation of C3, allowing C3 to target cells for elimination. In mice, C3 targets subsets of synapses and is required for synaptic elimination by microglia. In C4-deficient mice, fewer synaptic inputs are C3-positive
• A proposed mechanism that could explain the role of C4 in SZ is that elevated C4 levels could lead to EXCESSIVE and aberrant C3-mediated TARGETING of SYNAPSES, overactivity of microglia and subsequent loss of synapses and grey matter associated with SZ.