Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model
| Autor: | Annamalai Prakasam, Jason Lockrow, Heather A. Bimonte-Nelson, Kumar Sambamurti, Peng Huang, Ann-Charlotte Granholm |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Calbindins medicine.medical_specialty medicine.medical_treatment Tocopherols Trisomy Neuropathology Biology Article Choline O-Acetyltransferase Amyloid beta-Protein Precursor Mice Mice Neurologic Mutants Prosencephalon S100 Calcium Binding Protein G Developmental Neuroscience Internal medicine medicine Animals Memory disorder Cholinergic neuron Cognitive decline Maze Learning Analysis of Variance Memory Disorders Mice Inbred C3H Basal forebrain Vitamin E Age Factors Vitamins medicine.disease Chromosomes Mammalian Acetylcholine Disease Models Animal Memory Short-Term Neuroprotective Agents Endocrinology Gene Expression Regulation Neurology Nerve Degeneration Cholinergic Down Syndrome Alzheimer's disease Reactive Oxygen Species Psychomotor Performance |
| Zdroj: | Experimental Neurology. 216:278-289 |
| ISSN: | 0014-4886 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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