Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model.
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.
Lockrow
Jason
J
Department of Neuroscience, and the Center on Aging, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA.
Prakasam
Annamalai
A
Huang
Peng
P
Bimonte-Nelson
Heather
H
Sambamurti
Kumar
K
Granholm
Ann-Charlotte
AC
D000109:Acetylcholine / Q000378:metabolism; D000367:Age Factors; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D064026:Calbindins; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D033481:Chromosomes, Mammalian; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000150:complications* / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008818:Mice, Neurologic Mutants; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000209:etiology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D016548:Prosencephalon / Q000473:pathology; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D024505:Tocopherols / Q000008:administration & dosage*; D014314:Trisomy; D014815:Vitamins / Q000008:administration & dosage*
D016564:Amyloid beta-Protein Precursor; D064026:Calbindins; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D064030:S100 Calcium Binding Protein G; D014815:Vitamins; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine; D024505:Tocopherols