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Homer-1a immediate early gene expression correlates with better cognitive performance in aging

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Abstract

The molecular mechanisms underlying cognitive decline during healthy aging remain largely unknown. Utilizing aged wild-type C57BL/6 mice as a model for normal aging, we tested the hypothesis that cognitive performance, memory, and learning as assessed in established behavioral testing paradigms are correlated with the differential expression of isoforms of the Homer family of synaptic scaffolding proteins. Here we describe a loss of cognitive and motor function that occurs when Homer-1a/Vesl-1S protein levels drop during aging. Our data describe a novel mechanism of age-related synaptic changes contributing to loss of biological function, spatial learning, and memory formation as well as motor coordination, with the dominant negative uncoupler of synaptic protein clustering, Homer-1a/Vesl-1S, as a potential target for the prophylaxis and treatment of age-related cognitive decline.

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Acknowledgments

Research reported in this publication was supported in part by the National Institute on Aging and the National Center for Research Resources of the National Institutes of Health under the award numbers P01AG022550, P01AG027956 (MJF, NS, PK), P01AG010485, S10RR022570 and S10RR027093 (PK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support for this study was provided by the Felix and Carmen Sabates Missouri Endowed Chair in Vision Research, and the Vision Research Foundation of Kansas City (PK). The authors thank Jill Hilgenberg, Kathy Vernon and Amy Shah for excellent technical assistance and Margaret, Richard, and Sara Koulen for generous support and encouragement.

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Authors and Affiliations

  1. Department Ophthalmology and Vision Research Center, School of Medicine, University of Missouri—Kansas City, 2411 Holmes St., Kansas City, MO, 64108, USA

    Simon Kaja, Priscilla K. Borden, Nitasha Khullar, Maaz Iqbal, Julie L. Collins & Peter Koulen

  2. Department of Pharmacology and Neuroscience and Institute for Aging and Alzheimer’s Disease Research, University of North Texas Health Science Center, Fort Worth, TX, 76107, USA

    Nathalie Sumien & Michael J. Forster

  3. Department of Basic Medical Science, School of Medicine, University of Missouri—Kansas City, 2411 Holmes St., Kansas City, MO, 64108, USA

    Peter Koulen

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  1. Simon Kaja
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  2. Nathalie Sumien
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  4. Nitasha Khullar
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  8. Peter Koulen
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Correspondence to Peter Koulen.

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Kaja, S., Sumien, N., Borden, P.K. et al. Homer-1a immediate early gene expression correlates with better cognitive performance in aging. AGE 35, 1799–1808 (2013). https://doi.org/10.1007/s11357-012-9479-6

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  • DOI: https://doi.org/10.1007/s11357-012-9479-6

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