Oxidative damage increases with age in a canine model of human brain aging.
We assayed levels of lipid peroxidation, protein carbonyl formation, glutamine synthetase (GS) activity and both oxidized and reduced glutathione to study the link between oxidative damage, aging and beta-amyloid (Abeta) in the canine brain. The aged canine brain, a model of human brain aging, naturally develops extensive diffuse deposits of human-type Abeta. Abeta was measured in immunostained prefrontal cortex from 19 beagle dogs (4-15 years). Increased malondialdehyde (MDA), which indicates increased lipid peroxidation, was observed in the prefrontal cortex and serum but not in cerebrospinal fluid (CSF). Oxidative damage to proteins (carbonyl formation) also increased in brain. An age-dependent decline in GS activity, an enzyme vulnerable to oxidative damage, and in the level of glutathione (GSH) was observed in the prefrontal cortex. MDA level in serum correlated with MDA accumulation in the prefrontal cortex. Although 11/19 animals exhibited Abeta, the extent of deposition did not correlate with any of the oxidative damage measures, suggesting that each form of neuropathology accumulates in parallel with age. This evidence of widespread oxidative damage and Abeta deposition is further justification for using the canine model for studying human brain aging and neurodegenerative diseases.
Institute for Brain Aging and Dementia, University of California, Irvine, California 92697-4540, USA. ehead@uci.edu
E
E
Head
J
J
Liu
T M
TM
Hagen
B A
BA
Muggenburg
N W
NW
Milgram
B N
BN
Ames
C W
CW
Cotman
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism; D000818:Animals; D002555:Cerebrospinal Fluid / Q000737:chemistry; D004285:Dogs; D005974:Glutamate-Ammonia Ligase / Q000737:chemistry / Q000378:metabolism; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D019803:Glutathione Disulfide / Q000032:analysis / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000032:analysis / Q000378:metabolism; D010084:Oxidation-Reduction; D017397:Prefrontal Cortex / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D013995:Time
D016229:Amyloid beta-Peptides; D011506:Proteins; D008315:Malondialdehyde; D005974:Glutamate-Ammonia Ligase; D005978:Glutathione; D019803:Glutathione Disulfide