Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model

Jason Lockrow, Annamalai Prakasam, Peng Huang, Heather Bimonte-Nelson, Kumar Sambamurti, Ann Charlotte Granholm

Research output: Contribution to journalArticle

93 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)278-289
Number of pages12
JournalExperimental Neurology
Volume216
Issue number2
DOIs
StatePublished - Apr 2009

Keywords

  • Alpha-tocopherol
  • Alzheimer's disease
  • Basal forebrain cholinergic neuron
  • Calbindin D-28k
  • Neurodegeneration
  • Ts65Dn
  • Working memory

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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