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Oxidative damage increases with age in a canine model of human brain aging
Author(s) -
Head E.,
Liu J.,
Hagen T. M.,
Muggenburg B. A.,
Milgram N. W.,
Ames B. N.,
Cotman C. W.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.00969.x
Subject(s) - lipid peroxidation , oxidative stress , glutathione , malondialdehyde , endocrinology , medicine , oxidative phosphorylation , prefrontal cortex , brain damage , chemistry , human brain , neuropathology , biochemistry , biology , neuroscience , enzyme , cognition , disease
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 β‐amyloid (Aβ) in the canine brain. The aged canine brain, a model of human brain aging, naturally develops extensive diffuse deposits of human‐type Aβ. Aβ 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 Aβ, 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 Aβ deposition is further justification for using the canine model for studying human brain aging and neurodegenerative diseases.