Abstract
Introduction 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.
Methods 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.
Results 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.
Discussion 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.
Key words
C1q, Synaptic pruning, neuroinflammation, Alzheimer’s disease,
neurodegeneration
