PERFORANT PATH TRANSECTION INDUCES COMPLEMENT C9 DEPOSITION IN HIPPOCAMPUS

The presence of complement system proteins in amyloid plaques and the up-regulation of several complement mRNAs in neurons and glial cells i n affected brain regions during Alzheimer disease (AD) provided a basi s for further examination of complement protein expression in a rodent lesion model of AD. Perforant path transection in rats was used as a model for the degeneration of entorhinal cortex (EC) layer II neurons and the consequent deafferentation of the hippocampus that occurs duri ng AD. Immunostaining for C9, a key terminal component of the compleme nt cascade membrane attack complex (MAC), showed extracellular C9 depo sition in parenchyma around the EC wound and in hippocampus as early a s 1 day, and disappeared by 14 days postlesion. Apoptosis of EC layer II neurons was Seen and was presumably due to severing of their axonal projections to the hippocampus by the transection lesion. However, ap optotic EC layer II neurons were not immunostained by anti-rat C9 anti body, suggesting complement was not involved in inducing apoptosis. In the deafferented hippocampus, extracellular C9 immunostaining was loc alized to the dentate gyrus middle molecular layer, a region of synapt ic loss, dendritic degeneration, and early synaptogenesis. In addition , intracellular C9 immunostaining was seen only in select hippocampal interneurons. Dentate gyrus granule neurons and pyramidal neurons were not C9 immunostained. Clusterin (SGP-2), a soluble inhibitor of the M AC that is up-regulated in AD, was also detected in the wound area (ex tracellular), the dentate gyrus middle molecular layer (extracellular) , and intracellularly in scattered hippocampal interneurons. The data support the hypothesis that the complement system generally participat es in responses to brain injury, as well as in AD. (C) 1996 Academic P ress, Inc.