Occurrence of complement protein C3 in dying pyramidal neurons in rat hippocampus after systemic administration of kainic acid.
To evaluate the roles of complement in kainic acid (KA)-induced neuronal damages, the immunohistochemical localization of the complement protein C3 was examined in rat hippocampus after systemic KA injection. The immunoreactivity for C3 was found in glial cells in control rats, and such glial cells were increased in number after KA injection. Our confocal study showed that C3-positive glial cells were microglia. Three to seven days after KA, C3 immunoreactivity appeared in CA1 and CA3 pyramidal neurons. Double staining for C3 combined with the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling showed that occurrence of C3 immunoreactivity in neurons coincided well with that of DNA fragmentation. Western blot analysis and RT-PCR experiments suggested local synthesis of C3 by brain cells. Our results suggest that C3 contributes greatly to neuronal death after systemic KA administration, and that microglia and neurons are the local source of C3 in KA-induced brain injury.
Morita
Hiroyuki
H
Molecular Neuroscience Research Center, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga 520-2192, Japan.
Suzuki
Katsuaki
K
Mori
Norio
N
Yasuhara
Osamu
O
D000818:Animals; D015153:Blotting, Western; D040881:CD11a Antigen / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D051152:Clusterin / Q000378:metabolism; D003176:Complement C3 / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D018613:Microscopy, Confocal; D017966:Pyramidal Cells / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D040881:CD11a Antigen; D051152:Clusterin; D003176:Complement C3; D018690:Excitatory Amino Acid Agonists; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D007608:Kainic Acid