Solvent effects on beta protein toxicity in vivo.
Human beta (1-40) and rat beta (1-42) were dissolved in three different solvents and stereotaxically injected into rat hippocampus with the contralateral side injected with control reverse sequence peptide or vehicle alone. Results at 1 week showed gross toxicity of the 35% acetonitrile solvent which was markedly enhanced by 3 nmol of beta protein but not by reverse sequence peptide. Beta peptide in water also appeared more toxic than reverse sequence, but the results were less clear cut. In contrast, 3 nmol of beta peptide in a cyclodextrin/PBS solution produced no marked short-term toxic effects. Peripheral injection of substance P failed to prevent toxicity. We conclude that solvent effects play a major role in acute beta protein neurotoxicity.
Waite
J
J
University of California, San Diego 92093.
Cole
G M
GM
Frautschy
S A
SA
Connor
D J
DJ
Thal
L J
LJ
D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001921:Brain; D003505:Cyclodextrins; D006624:Hippocampus / Q000473:pathology; D006651:Histocytochemistry; D006801:Humans; D007267:Injections; D009422:Nervous System Diseases / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D012995:Solubility; D012997:Solvents
D016229:Amyloid beta-Peptides; D003505:Cyclodextrins; D012997:Solvents