Prevention of age-related spatial memory deficits in a transgenic mouse model of Alzheimer's disease by chronic Ginkgo biloba treatment.
Alzheimer's disease (AD) is characterized by cognitive decline and deposition of beta-amyloid (Abeta) plaques in cortex and hippocampus. A transgenic mouse AD model (Tg2576) that overexpresses a mutant form of human Abeta precursor protein exhibits age-related cognitive deficits, Abeta 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 Abeta and hippocampal Abeta 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 Abeta levels and without suppressing protein oxidation in a transgenic mouse model of AD.
Stackman
Robert W
RW
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239-3098, USA. stackman@ohsu.edu
Eckenstein
Felix
F
Frei
Balz
B
Kulhanek
Doris
D
Nowlin
Jessica
J
Quinn
Joseph F
JF
D000375:Aging / Q000523:psychology*; D000544:Alzheimer Disease / Q000523:psychology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000686:Amyloidosis / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D001923:Brain Chemistry; D005260:Female; D020441:Ginkgo biloba; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D008517:Phytotherapy; D058225:Plaque, Amyloid / Q000473:pathology; D011247:Pregnancy; D013028:Space Perception / Q000187:drug effects*
D016229:Amyloid beta-Peptides; D009419:Nerve Tissue Proteins