Dataset Information

Fc Gamma Receptor (FcγR) Expression and Signaling in the Developing Rat Brain

ABSTRACT: 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 (FcγR) 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 FcγR in the developing brain. Thus, we first investigated FcγR 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 IFNγ. In order to confirm protein abundance of FcγRIa, FcγRIIb and FcγRIIIa 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 FcγRIa and the inhibitory FcγRIIb. Functional analysis shows that exposure of hippocampal and cortical cell cultures to IgG-IC increased intracellular calcium and Erk phosphorylation, and triggered FcγR-mediated internalization of IgG. Collectively, these data demonstrate that developing neurons and astrocytes express signaling competent FcγR. which could establish a molecular mode of action of maternal antibodies could influence vulnerability to neurodevelopmental disorders via direct interactions with FcγR 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 FcγR on non-immune cells in the developing brain.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Hippocampal Neuron, Cell Culture

SUBMITTER: Marc van Oostrum

LAB HEAD: Bernd Wollscheid

PROVIDER: PXD006904 | Pride | 2018-01-11

REPOSITORIES: Pride

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			Action	DRS
	marcv_X1609_009.raw	Raw
	marcv_X1609_010.raw	Raw
	marcv_X1609_011.raw	Raw
	marcv_x1609_009.glyco.interact.prot.xml	Xml
	marcv_x1609_010.glyco.interact.prot.xml	Xml

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Publications

Fc gamma receptors are expressed in the developing rat brain and activate downstream signaling molecules upon cross-linking with immune complex.

Stamou Marianna M Grodzki Ana Cristina AC van Oostrum Marc M Wollscheid Bernd B Lein Pamela J PJ

Journal of neuroinflammation 20180106 1

<h4>Background</h4>Exposure of the developing brain to immune mediators, including antibodies, is postulated to increase risk for neurodevelopmental disorders and neurodegenerative disease. It has been suggested that immunoglobulin G-immune complexes (IgG-IC) activate Fc gamma receptors (FcγR) expressed on neurons to modify signaling events in these cells. However, testing this hypothesis is hindered by a paucity of data regarding neuronal FcγR expression and function.<h4>Methods</h4>FcγR transc ...[more]

PMID: 29306331

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