Age-related losses of cognitive function and motor skills in mice are associated with oxidative protein damage in the brain

Michael J. Forster, Anju Dubey, Kimberly M. Dawson, William A. Stutts, Harbans Lal, Rajindar S. Sohal

Research output: Contribution to journalArticle

387 Scopus citations

Abstract

The hypothesis that age-associated impairment of cognitive and motor functions is due to oxidative molecular damage was tested in the mouse. In a blind study, senescent mice (aged 22 months) were subjected to a battery of behavioral tests for motor and cognitive functions and subsequently assayed for oxidative molecular damage as assessed by protein carbonyl concentration in different regions of the brain. The degree of age-related impairment in each mouse was determined by comparison to a reference group of young mice (aged 4 months) tested concurrently on the behavioral battery. The age- related loss of ability to perform a spatial swim maze task was found to be positively correlated with oxidative molecular damage in the cerebral cortex, whereas age-related loss of motor coordination was correlated with oxidative molecular damage within the cerebellum. These results support the view that oxidative stress is a causal factor in brain senescence. Furthermore, the findings suggest that age-related declines of cognitive and motor performance progress independently, and involve oxidative molecular damage within different regions of the brain.

Original languageEnglish
Pages (from-to)4765-4769
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number10
DOIs
StatePublished - 14 May 1996

Keywords

  • brain function
  • memory
  • oxidative stress
  • protein oxidative damage

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