Title: Fc Gamma Receptor Expression and Signaling in the Developing Rat Brain

Accession Number: PXD006904

Link to Dataset: https://www.ebi.ac.uk/pride/archive/projects/PXD006904

Repository: PRIDE Archive

Data Type(s): Proteomics

Experiment Type(s): Shotgun proteomics

Organism(s): Rattus norvegicus

Summary: Maternal antibodies specific for antigens in the developing brain are implicated as risk factors for neurodevelopmental disorders, but how these antibodies interfere with neurodevelopment remain speculative. It has been postulated that immunoglobulin G-immune complexes (IgG-IC) activate Fc gamma receptors (Fc R) on non-immune cells in the brain, thereby modulating intracellular signaling and/or internalizing function-blocking antibodies specific for intracellular antigens. However, testing this hypothesis has been hindered by the paucity of data regarding Fc R in the developing brain. Thus, we first investigated Fc R expression in the brain of neonatal male and female rats using quantitative PCR analyses. FcgrIa, FcgrIIa, FcgrIIb, FcgrIIIa and Fcgrt transcripts were detectable in the cortex, hippocampus and cerebellum at postnatal days 1 and 7. These transcripts were also present in primary hippocampal and cortical cell cultures, where their expression was upregulated by IFN . In order to confirm protein abundance of Fc RIa, Fc RIIb and Fc RIIIa in cultured hippocampal and cortical neurons and astrocytes on the single cell and tissue level we used immunocytochemistry, western blotting, proteotype analysis, and flow cytometry. The data shows that a subpopulation of these cells co-express the excitatory Fc RIa and the inhibitory Fc RIIb. Functional analysis shows that exposure of hippocampal and cortical cell cultures to IgG-IC increased intracellular calcium and Erk phosphorylation, and triggered Fc R-mediated internalization of IgG. Collectively, these data demonstrate that developing neurons and astrocytes express signaling competent Fc R. which could establish a molecular mode of action of maternal antibodies could influence vulnerability to neurodevelopmental disorders via direct interactions with Fc R on non-immune cells in the developing brain. These findings support the hypothesis that maternal antibodies influence vulnerability to neurodevelopmental disorders via direct interactions with Fc R on non-immune cells in the developing brain.

Publication(s) associated with this dataset:

• Stamou M, Grodzki A, van Oostrum M, Wollscheid B, Lein PJ. 2018. Fc gamma receptors are expressed in the developing rat brain and activate downstream signaling molecules upon cross-linking with immune complex. J Neuroinflammation 15:7. doi:10.1186/s12974-017-1050-z PMID:29306331 PMCID:PMC5756609

Project(s) associated with this dataset:

• None at this time