Morphological Representation of C1q in the Aging Central Nervous System

The complement protein C1q is essential for the innate immune system and neurophysiological and neuropathological processes. To gain more insight into these functions in the CNS, a comprehensive understanding of the morphological representation, especially of its cellular and subcellular target structures, is of great importance.

For a free-floating preparation, the brains of wild-type and ArcAβ mice were cut into 100 μm slices. Living slices were incubated in Ringer's solution and then fixed in 4% paraformaldehyde (PFA) and stained with different primary and secondary antibodies or methoxy-X04.

C1q was abundant in the entire brain. Interestingly, C1q accumulated around cell nuclei, with a perineuronal localization around neuronal somata and a paraneuronal accumulation around non-neuronal cells, e. g., microglia. Moreover, dendritic-like, linear, branched C1q signals were observed in the area between the dentate gyrus and the CA1 region of the hippocampus. Complementary staining revealed an overlap with β-amyloid accumulation reflected by the deposition of C1q within plaques and modified basal C1q levels in the brains of transgenic ArcAβ animals.

The applied free-floating approach is suitable for C1q immunofluorescence imaging. The consistent colocalization of the complement protein C1q with β-amyloid plaques may reflect an activated immune response, whereas the accumulation of C1q around neuronal structures such as somata and dendrites is still a matter of debate. Intriguingly, C1q surrounds those structures in older brains of both wild-type and ArcAβ mice. Our results also indicate an involvement of C1q in neurophysiological and neurodegenerative processes.