An immune factor in the brain plays critical roles in neuron function and aging

Amazing stuff!

"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 ... suggest C1q may be involved in age-related cognitive changes and neurodegenerative conditions. ...
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. ..."

From the highlights and abstract:

"Highlights

• Microglial C1q accumulates in neuronal ribonucleoprotein (RNP) complexes across aging

• C1q protein undergoes RNA-mediated liquid-liquid phase separation

• RNA is necessary for C1q interactions with neuronal RNP complexes in vivo

• Adult C1qKO mice have elevated neuronal translation and altered brain proteostasis

Summary

Neuroimmune interactions mediate intercellular communication and underlie critical brain functions. Microglia, CNS-resident macrophages, modulate the brain through direct physical interactions and the secretion of molecules. One such secreted factor, the complement protein C1q, contributes to complement-mediated synapse elimination in both developmental and disease models, yet brain C1q protein levels increase significantly throughout aging. Here, we report that C1q interacts with neuronal ribonucleoprotein (RNP) complexes in an age-dependent manner. Purified C1q protein undergoes RNA-dependent liquid-liquid phase separation (LLPS) in vitro, and the interaction of C1q with neuronal RNP complexes in vivo is dependent on RNA and endocytosis. Mice lacking C1q have age-specific alterations in neuronal protein synthesis in vivo and impaired fear memory extinction. Together, our findings reveal a biophysical property of C1q that underlies RNA- and age-dependent neuronal interactions and demonstrate a role of C1q in critical intracellular neuronal processes."

An immune factor in the brain plays critical roles in neuron function and aging | Broad Institute "Study highlights unexpected interactions between innate immune system and neurons, raises questions about additional roles for immune system in the brain with aging."

Microglial-derived C1q integrates into neuronal ribonucleoprotein complexes and impacts protein homeostasis in the aging brain (open access)

Graphical abstract

C1q, produced by microglia (green and blue), interacts with neurons (purple and blue).