Implants containing beta-amyloid protein are not neurotoxic to young and old rat brain.
Because the cellular effects of beta-amyloid protein (beta-AP) are currently unclear, we evaluated the in vivo effects of beta-AP implants in a lipid matrix to prolong tissue exposure in the brains of rats. Young 3-month-old rats and aged 18-month-old rats received implants of beta-AP prepared in a cocoa butter matrix in the dorsal hippocampus and corpus striatum on one side of the brain and implants of either prolactin or scrambled beta-AP peptide in cocoa butter on the contralateral side. The old rats also received implants of beta-AP embedded in a cholesterol matrix or cholesterol alone in the frontal cortex. The young rats were sacrificed 3-4 days after implantation, while the old rats were sacrificed 6-8 weeks after implantation. Lesion size on the beta-AP implanted side did not differ significantly from lesion size observed with control peptides. Bielschowsky silver staining revealed few argyrophilic neurites and axonal spheroids associated with either beta-AP or control implants. Alz 50 and ubiquitin immunoreactivity were not observed. None of the implant sites demonstrated cytopathology characteristic of Alzheimer's disease. The results of this study indicate that beta-AP implantation into the brains of rats produced no consistent effect beyond that seen with control peptide implants.
Clemens
J A
JA
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285.
Stephenson
D T
DT
D000375:Aging / Q000473:pathology*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D003342:Corpus Striatum / Q000473:pathology; D004343:Drug Implants; D006624:Hippocampus / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D004343:Drug Implants