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Gene-expression profile of the ageing brain in mice

Nature Genetics volume 25, pages 294–297 (2000)Cite this article

Abstract

Ageing of the brain leads to impairments in cognitive and motor skills, and is the major risk factor for several common neurological disorders such as Alzheimer disease (AD) and Parkinson disease (PD). Recent studies suggest that normal brain ageing is associated with subtle morphological and functional alterations in specific neuronal circuits, as opposed to large-scale neuronal loss1. In fact, ageing of the central nervous system in diverse mammalian species shares many features, such as atrophy of pyramidal neurons, synaptic atrophy, decrease of striatal dopamine receptors, accumulation of fluorescent pigments, cytoskeletal abnormalities, and reactive astrocytes and microglia2. To provide the first global analysis of brain ageing at the molecular level, we used oligonucleotide arrays representing 6,347 genes to determine the gene-expression profile of the ageing neocortex and cerebellum in mice. Ageing resulted in a gene-expression profile indicative of an inflammatory response, oxidative stress and reduced neurotrophic support in both brain regions. At the transcriptional level, brain ageing in mice displays parallels with human neurodegenerative disorders. Caloric restriction, which retards the ageing process in mammals, selectively attenuated the age-associated induction of genes encoding inflammatory and stress responses.

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Figure 1: A comparative ratio analysis by oligonucleotide microarray hybridization and RTQ–PCR amplification of a subset of genes increased in expression in neocortex of old mice.

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Acknowledgements

This work was supported by NIH grants P01 AG11915 (R.W.) and R01 CA 78723 (T.A.P.). T.A.P. is a recipient of the Shaw Scientist (Milwaukee Foundation), Burroughs Wellcome Young Investigator and Basil O'Connor (March of Dimes) awards.

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Authors and Affiliations

  1. Environmental Toxicology Center, University of Wisconsin, Madison, Wisconsin, USA

    Cheol-Koo Lee

  2. Departments of Genetics and Medical Genetics, University of Wisconsin, Madison, Wisconsin, USA

    Cheol-Koo Lee & Tomas A. Prolla

  3. Department of Medicine and Wisconsin Regional Primate Research Center, University of Wisconsin, and Veterans Administration Hospital, Geriatric Research, Education and Clinical Center, Madison, Wisconsin, USA

    Richard Weindruch

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  1. Cheol-Koo Lee
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Correspondence to Richard Weindruch or Tomas A. Prolla.

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Lee, CK., Weindruch, R. & Prolla, T. Gene-expression profile of the ageing brain in mice. Nat Genet 25, 294–297 (2000). https://doi.org/10.1038/77046

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