Beta-amyloid deposition in the brains of rats chronically infused with thiorphan or lipopolysaccharide: the role of ascorbic acid in the vehicle.
Beta-amyloid deposition and neuroinflammation are two important features of Alzheimer's disease (AD) that may influence its progression. Chronic infusion of lipopolysaccharide (LPS) into the rodent 4th ventricle reproduces many of the neurobiological changes seen in AD. Chronic infusion of ascorbic acid containing thiorphan, an inhibitor of the enzyme neprilysin that catabolizes beta-amyloid, into the hippocampus induces extracellular deposition of beta-amyloid fibrils. We investigated whether the combined presence of chronic neuroinflammation could exacerbate the deposition of beta-amyloid induced by thiorphan. The infusion of any solution containing ascorbic acid alone or with thiorphan or LPS increased the level of intraneuronal beta-amyloid immunoreactivity. Solutions that did not contain ascorbic acid were not associated with increased intraneuronal beta-amyloid immunoreactivity. The role of neprilysin in the deposition of beta-amyloid in AD brains remains undetermined.
Hauss-Wegrzyniak
Beatrice
B
Arizona Research Laboratories, Division of Neural Systems, Memory & Aging, University of Arizona, Tucson, AZ 85724, USA.
Wenk
Gary L
GL
D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000502:physiology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D007260:Infusion Pumps; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D014677:Pharmaceutical Vehicles; D011480:Protease Inhibitors / Q000008:administration & dosage; D051381:Rats; D011916:Rats, Inbred F344; D015244:Thiorphan / Q000008:administration & dosage*
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D008070:Lipopolysaccharides; D014677:Pharmaceutical Vehicles; D011480:Protease Inhibitors; D015244:Thiorphan; D001205:Ascorbic Acid