Complement mRNA in the mammalian brain: responses to Alzheimer's disease and experimental brain lesioning.
This study describes evidence in the adult human and rat brain for mRNAs that encode two complement (C) proteins, C1qB and C4. C proteins are important effectors of humoral immunity and inflammation in peripheral tissues but have not been considered as normally present in brain. Previous immunocytochemical studies showed that C proteins are associated with plaques, tangles, and dystrophic neurites in Alzheimer's disease (AD), but their source is unknown. Combined immunocytochemistry and in situ hybridization techniques show C4 mRNA in pyramidal neurons and C1qB mRNA in microglia. Primary rat neuron cultures also show C1qB mRNA. In the cortex from AD brains, there were two- to threefold increases of C1qB mRNA and C4 mRNA, and increased C1qB mRNA prevalence was in part associated with microglia. As a model for AD, we examined entorhinal cortex perforant path transection in the rat brain, which caused rapid increases of C1qB mRNA in the ipsilateral, but not contralateral, hippocampus and entorhinal cortex. The role of brain-derived acute and chronic C induction during AD and experimental lesions can now be considered in relation to functions of C proteins that pertain to cell degeneration and/or cell preservation and synaptic plasticity.
Neurogerontology Division, Andrus Gerontology Center, University of Southern California, Los Angeles 90089-0191.
S A
SA
Johnson
M
M
Lampert-Etchells
G M
GM
Pasinetti
I
I
Rozovsky
C E
CE
Finch
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000302:isolation & purification; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000473:pathology / Q000502:physiology*; D001923:Brain Chemistry / Q000502:physiology*; D002352:Carrier Proteins / Q000096:biosynthesis; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000473:pathology; D003001:Cloning, Molecular; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008969:Molecular Sequence Data; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats
D000906:Antibodies; D002352:Carrier Proteins; D012333:RNA, Messenger; C020723:citrate-binding transport protein; D010751:Phosphopyruvate Hydratase