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Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model
Authors:Jason Lockrow  Annamalai Prakasam  Peng Huang  Heather Bimonte-Nelson  Kumar Sambamurti  Ann-Charlotte Granholm  
Institution:aDepartment of Neuroscience, and the Center on Aging, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA;bOncology Biostatistics Division, Johns Hopkins University, Baltimore Maryland, 21205, USA;cDepartment of Psychology, Behavioral Neuroscience Division, Arizona State University, Tempe, AZ 85287, USA;dArizona Alzheimer's Consortium, USA
Abstract:Down syndrome (DS) individuals develop several neuropathological hallmarks seen in Alzheimer's disease, including cognitive decline and the early loss of cholinergic markers in the basal forebrain. These deficits are replicated in the Ts65Dn mouse, which contains a partial trisomy of murine chromosome 16, the orthologous genetic segment to human chromosome 21. Oxidative stress levels are elevated early in DS, and may contribute to the neurodegeneration seen in these individuals. We evaluated oxidative stress in Ts65Dn mice, and assessed the efficacy of long-term antioxidant supplementation on memory and basal forebrain pathology. We report that oxidative stress was elevated in the adult Ts65Dn brain, and that supplementation with the antioxidant vitamin E effectively reduced these markers. Also, Ts65Dn mice receiving vitamin E exhibited improved performance on a spatial working memory task and showed an attenuation of cholinergic neuron pathology in the basal forebrain. This study provides evidence that vitamin E delays onset of cognitive and morphological abnormalities in a mouse model of DS, and may represent a safe and effective treatment early in the progression of DS neuropathology.
Keywords:Ts65Dn  Basal forebrain cholinergic neuron  Working memory  Alzheimer's disease  Neurodegeneration  Calbindin D-28k  Alpha-tocopherol
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