Prevention of age-related spatial memory deficits in a transgenic mouse model of Alzheimer's disease by chronic Ginkgo biloba treatment

Robert W. Stackman, Felix Eckenstein, Balz Frei, Doris Kulhanek, Jessica Nowlin, Joseph F. Quinn

Research output: Contribution to journalArticle

207 Scopus citations

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 languageEnglish (US)
Pages (from-to)510-520
Number of pages11
JournalExperimental Neurology
Volume184
Issue number1
DOIs
StatePublished - Nov 2003

Keywords

  • Alzheimer
  • Amyloid
  • Antioxidant
  • Hippocampus
  • Oxidative stress
  • Spatial learning
  • Spatial memory
  • Tg2576

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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