Complement C1q expression induced by Abeta in rat hippocampal organotypic slice cultures.
Amyloid beta peptide (Abeta) is a major component of senile plaques, one of the principle pathological features in Alzheimer's disease (AD) brains. Fibrillar Abeta has been shown to bind C1 via C1q, the recognition component of the classical complement pathway, resulting in the activation of the complement pathway, thereby initiating an inflammatory cascade in the brain. C1q has also been shown to enhance phagocytic activities of microglia, which could benefit in clearance of apoptotic cells or cellular debris. To begin to define the role of C1q in tissue injury mediated by Abeta, we assessed the appearance of C1q in hippocampal slice cultures treated with freshly solubilized or fibrillar Abeta 1-42. Here we demonstrate a dose- and time-dependent uptake of exogenously applied Abeta by pyramidal neurons in organotypic slice cultures from rat hippocampus. Importantly, when slices were immunostained with antibody against rat C1q, a distinct reactivity for C1q in cells within the neuronal cell layer of cornu ammonis (CA) of hippocampus, primarily the CA1/CA2, was observed in the Abeta-treated slices. No such immunoreactivity was detected in untreated cultures or upon addition of control peptides. ELISA assays also showed an increase in C1q in tissue extracts from slices of the treated group. Similarly, the mRNA level of C1q in slices was increased within 24 h after Abeta treatment. These data demonstrate that upon exposure to Abeta, C1q is expressed in neurons in this organotypic system. The induction of C1q may be an early, perhaps beneficial, tissue or cellular response to injury triggered by particular pathogenic stimuli.
Fan
Rong
R
Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697, USA.
Tenner
Andrea J
AJ
D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D015922:Complement C1q / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D012333:RNA, Messenger; D015922:Complement C1q