Abstract
Alzheimer's disease (AD) is characterized by cognitive decline and deposition of β-amyloid (Aβ) plaques in cortex and hippocampus. A transgenic mouse AD model (Tg2576) that overexpresses a mutant form of human Aβ precursor protein exhibits age-related cognitive deficits, Aβ plaque deposition, and oxidative damage in the brain. We tested the ability of Ginkgo biloba, a flavonoid-rich antioxidant, to antagonize the age-related behavioral impairment and neuropathology exhibited by Tg2576 mice. At 8 months of age, 16 female Tg2576 and 15 female wild-type (wt) littermate mice were given ad lib access to tap water or Ginkgo biloba (70 mg/kg/day in water). After 6 months of treatment, all mice received Morris water maze training (4 trials/day for 10 days) to assess hippocampal dependent spatial learning. All mice received a 60-s probe test of spatial memory retention 24 h after the 40th trial. Untreated Tg2576 mice exhibited a spatial learning impairment, relative to wt mice, while Ginkgo biloba-treated Tg2576 mice exhibited spatial memory retention comparable to wt during the probe test. Spatial learning was not different between Ginkgo biloba-treated and untreated wt mice. There were no group differences in learning to swim to a visible platform. Soluble Aβ and hippocampal Aβ plaque burden did not differ between the Tg2576 groups. Brain levels of protein carbonyls were paradoxically elevated in Ginkgo biloba-treated mice. These data indicate that chronic Ginkgo biloba treatment can block an age-dependent decline in spatial cognition without altering Aβ levels and without suppressing protein oxidation in a transgenic mouse model of AD.
Original language | English (US) |
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Pages (from-to) | 510-520 |
Number of pages | 11 |
Journal | Experimental Neurology |
Volume | 184 |
Issue number | 1 |
DOIs | |
State | Published - Nov 2003 |
Keywords
- Alzheimer
- Amyloid
- Antioxidant
- Hippocampus
- Oxidative stress
- Spatial learning
- Spatial memory
- Tg2576
ASJC Scopus subject areas
- Neurology
- Developmental Neuroscience