TY - JOUR
T1 - Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model
AU - Lockrow, Jason
AU - Prakasam, Annamalai
AU - Huang, Peng
AU - Bimonte-Nelson, Heather
AU - Sambamurti, Kumar
AU - Granholm, Ann Charlotte
N1 - Funding Information:
This work was supported by United States Public Health Service (AG12122) and the Anna and John J. Sie Foundation for Down Syndrome. We thank Muriel T. Davisson for the gift of breeding stocks and Dr. Louis Reichardt for the generous gift of TrkA antibodies. In addition, we thank Dr. Lauren Willis and Dr. Heather Boger for valuable scientific discussions and Selena Sumner, Alfred Moore, and Claudia Umphlet for outstanding technical assistance.
PY - 2009/4
Y1 - 2009/4
N2 - 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.
AB - 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.
KW - Alpha-tocopherol
KW - Alzheimer's disease
KW - Basal forebrain cholinergic neuron
KW - Calbindin D-28k
KW - Neurodegeneration
KW - Ts65Dn
KW - Working memory
UR - http://www.scopus.com/inward/record.url?scp=62049085639&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=62049085639&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2008.11.021
DO - 10.1016/j.expneurol.2008.11.021
M3 - Article
C2 - 19135442
AN - SCOPUS:62049085639
SN - 0014-4886
VL - 216
SP - 278
EP - 289
JO - Experimental Neurology
JF - Experimental Neurology
IS - 2
ER -