COMPLEMENT AND GLUTAMATE NEUROTOXICITY - GENOTYPIC INFLUENCES OF C5 IN A MOUSE MODEL OF HIPPOCAMPAL NEURODEGENERATION

Using mice genetically deficient in the complement (C)-system componen t C5, this study explored a potential novel role of the C-system in Ca 2+-mediated control of glutamate AMPA receptor functions. We found tha t Ca2+ preincubation of frozen brain tissue sections enhances AMPA bin ding capacity more dynamically in C5 deficient (C5(-)) than congenic C 5 sufficient (C5(+)) mice. The Ca2+-mediated response was mostly local ized to the CA3 and CA1 subdivisions of the pyramidal layers of the hi ppocampal formation. Ln C5(-) mice, kainic acid (KA) excitotoxicity th at models hippocampal neurodegeneration abolished the Ca2+-mediated in duction of hippocampal AMPA binding. The changes in AMPA binding prece ded temporally and overlapped anatomically the appearance of apoptotic features in the same hippocampal neuron layers. C5(-) mice showed gre ater hippocampal neurodegeneration then C5(+) mice. NMDA binding contr olled for specificity of glutamate-mediated changes and found no C5 ge notypic influences. The study gives further credence to the role of th e C-system in modifying the intensity and outcome during response to c onditions leading to hippocampal neurodegeneration.