Analysis of brain injury following intrahippocampal administration of beta-amyloid in streptozotocin-treated rats.
It has been suggested that the vulnerability of the aged brain to Alzheimer's disease (AD) pathogenesis depends on a number of risk factors, including abnormal glycolytic metabolism and beta-amyloid accumulation. Intrahippocampal injections of beta-amyloid and related peptides were administered to chronically hyperglycemic rats to examine beta-amyloid toxicity and the interaction with imbalances of glucose metabolism. Chronic hyperglycemia was induced by systemic injection of streptozotocin (STZ) which selectively destroys pancreatic beta-islet cells. Ten days after intrahippocampal injection of synthetic beta-amyloid peptides (beta 1-42, beta 25-35, scrambled beta 25-35), lesion volume, blood glucose, and plasma corticosterone concentrations, beta 1-42 immunoreactivity and gliosis were assessed to determine peptide toxicity in the normoglycemic and hyperglycemic conditions. Glucose levels correlated with plasma corticosterone concentrations (r = 0.85) and increased lesion volume size (r = 0.36). Intrahippocampal peptide injections in normoglycemic subjects did not induce significant damage as compared to control injections of vehicle alone. STZ-treated groups demonstrated a trend for increased lesion volume size following injection of either vehicle, beta 1-42, or beta 25-35. The combination of the beta 1-42 peptide and streptozotocin-induced hyperglycemia was toxic and induced significantly larger lesions (p < 0.01) of the dorsal blade of the dentate gyrus as compared to injections of beta 1-42 into normoglycemic subjects.
Smyth
M D
MD
Irvine Research Unit in Brain Aging, University of California 92717.
Kesslak
J P
JP
Cummings
B J
BJ
Cotman
C W
CW
D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000473:pathology*; D003345:Corticosterone / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D005911:Gliosis / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D007267:Injections; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D005947:Glucose; D003345:Corticosterone