Immune cells in the central nervous system called microglia produce a protein called C1q, which helps the immune system prune synapses (the junctions between neurons) in the developing brain. A new study reveals that C1q can also enter neurons, where it influences protein production, and can accumulate within neurons over time. These new findings — published in Cell by researchers at Boston Children's Hospital and the Broad Institute of MIT and Harvard — suggest C1q may be involved in age-related cognitive changes and neurodegenerative conditions. 

C1q is a component of the innate immune system and, in the brain, mediates interactions between microglia and cells of the nervous system. The amount of C1q in the brain increases with age in both people and mice, but how that relates to brain function has been unclear. 

Using a broad approach, Nicole Scott-Hewitt — a postdoctoral fellow in the lab of Beth Stevens, a research associate in neurobiology at Boston Children’s Hospital and an institute member and Merkin Institute fellow at the Broad — and colleagues discovered that neurons can take in C1q protein from outside the cell through a process called endocytosis, a surprising finding as it showed the presence within neurons of what was thought to be an external mediator of neuron function.

Scott-Hewitt, Stevens, and colleagues in Broad's Proteomics Platform and elsewhere also saw that upon gaining entrance to the neuron, C1q interacts with RNA-binding proteins, accumulating in neurons' ribonucleoprotein complexes and sparking both a significant increase in protein production and a change in the balance of proteins within the adult brain. These changes, which suggest that C1q may be important for keeping the brain's proteins in check, were age-specific, with noticeable differences in protein production in adult mice compared to younger ones. Additional studies revealed that the loss of C1q affected the ability of adult mice to forget fearful experiences.

Taken together, the team's findings indicate that C1q produced in the brain can also influence neurons' internal functions, independent of its previously described role in synapse pruning. They also suggest that C1q influences learning, memory, and flexibility in the adult brain, potentially by interacting with specific complexes within neurons that impact protein production.

Adapted from a press release issued by Boston Children's Hospital.