Complement and glutamate neurotoxicity. Genotypic influences of C5 in a mouse model of hippocampal neurodegeneration.
Using mice genetically deficient in the complement (C)-system component C5, this study explored a potential novel role of the C-system in Ca(2+)-mediated control of glutamate AMPA receptor functions. We found that Ca2+ preincubation of frozen brain tissue sections enhances AMPA binding capacity more dynamically in C5 deficient (C5-) than congenic C5 sufficient (C5+) mice. The Ca(2+)-mediated response was mostly localized to the CA3 and CA1 subdivisions of the pyramidal layers of the hippocampal formation. In C5- mice, kainic acid (KA) excitotoxicity that models hippocampal neurodegeneration abolished the Ca(2+)-mediated induction of hippocampal AMPA binding. The changes in AMPA binding preceded temporally and overlapped anatomically the appearance of apoptotic features in the same hippocampal neuron layers. C5- mice showed greater hippocampal neurodegeneration then C5+ mice. NMDA binding controlled for specificity of glutamate-mediated changes and found no C5 genotypic influences. The study gives further credence to the role of the C-system in modifying the intensity and outcome during response to conditions leading to hippocampal neurodegeneration.
Tocco
G
G
Hedco Neuroscience Program, USC, Los Angeles, USA.
Musleh
W
W
Sakhi
S
S
Schreiber
S S
SS
Baudry
M
M
Pasinetti
G M
GM
D000818:Animals; D001345:Autoradiography; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003182:Complement C5 / Q000172:deficiency / Q000235:genetics*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005838:Genotype; D018698:Glutamic Acid / Q000633:toxicity*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D018091:Receptors, AMPA / Q000378:metabolism
D003182:Complement C5; D018690:Excitatory Amino Acid Agonists; D018091:Receptors, AMPA; D018698:Glutamic Acid; D007608:Kainic Acid; D002118:Calcium