Expression of C5a receptor in mouse brain: role in signal transduction and neurodegeneration

• Published in: Neuroscience Vol. 88; no. 4; pp. 1073 - 1082
• Main Authors: Osaka, H., McGinty, A., Höpken, U.E., Lu, B., Gerard, C., Pasinetti, G.M.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-02-1999; Elsevier
• Subjects: Alzheimer's disease; anaphylatoxin; Animals; astrocytes; Biochemistry and metabolism; Biological and medical sciences; Brain - cytology; Brain - metabolism; Brain Diseases - chemically induced; Brain Diseases - metabolism; Cells, Cultured; Central nervous system; complement; Complement C5a - genetics; Complement C5a - metabolism; Complement C5a - pharmacology; complement component C5a receptors; Fundamental and applied biological sciences. Psychology; Humans; Kainic Acid; kinase; Male; Mice; Mice, Inbred Strains; Mice, Knockout - genetics; Nerve Degeneration - physiopathology; Neuroglia - metabolism; Neurons - metabolism; Receptors, Complement - metabolism; Receptors, Complement - physiology; Recombinant Proteins; RNA, Messenger - metabolism; Signal Transduction - physiology; Vertebrates: nervous system and sense organs; KA, kainic acid; SDS-PAGE, SDS-polyacrylamide gel electrophoresis; HEPES, N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid; ERK kinase, mitogen-activated extracellular signal-regulated kinase; TEA, tetraethlyammonium; DMEM, Dulbecco's modified essential medium; MEK-1, MAP kinase kinase; SSC, standard saline citrate; SDS, sodium dodecyl sulfate; kinase; MBP, myelin basic protein; PBS, phosphate-buffered saline; AD, Alzheimer's disease; EGTA, ethyleneglycolbis(aminoethyl-ether)tetra-acetate; MAP kinase, mitogen-activated protein kinase; hr, human recombinant; astrocytes; complement; anaphylatoxin; Alzheimer's disease; C5aR, C5a anaphylatoxin receptor; Enzyme; Transferases; Rodentia; Central nervous system; C5a Complement; Astrocyte; Gene expression; Signal transduction; Vertebrata; Mammalia; Mouse; Kinase; Lesion; Kainic acid; Brain (vertebrata); Biological receptor
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(98)00372-8

In this study we explored the potential role of the complement derived anaphylatoxin C5a and the expression of its receptor in mouse brain. Using
in situ hybridization, we found that C5a receptor messenger RNA is expressed in mouse brain. In response to intraventricular kainic acid injection, there was marked increase in the C5a receptor messenger RNA expression, particularly in hippocampal formation and cerebral cortex. C5a ligand-binding autoradiography confirmed the functional expression and elevation of the C5a receptor post-lesioning. The expression of C5a receptor messenger RNA in brain was confirmed by northern blot hybridization of total RNA from neuronal and glial cells
in vitro. Based on these findings we explored the role of C5a in mechanisms of signal transduction in brain cells. Treatment of primary cultures of mouse astrocytes with human recombinant C5a resulted in the activation of mitogen-activated extracellular signal-regulated protein kinase. This response appeared to be mediated by the C5a receptor since astrocyte cultures derived from C5a receptor knockout mice were not responsive to the treatment. Understanding the regulation of C5a receptor in brain and mechanisms by which pro-inflammatory C5a modulates specific signal transduction pathways in brain cells is crucial to studies of inflammatory mechanisms in neurodegeneration.