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Environmental Enrichment Improves Behavior, Cognition, and Brain Functional Markers in Young Senescence-Accelerated Prone Mice (SAMP8)

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Abstract

The environment in which organisms live can greatly influence their development. Consequently, environmental enrichment (EE) is progressively recognized as an important component in the improvement of brain function and development. It has been demonstrated that rodents raised under EE conditions exhibit favorable neuroanatomical effects that improve their learning, spatial memory, and behavioral performance. Here, by using senescence-accelerated prone mice (SAMP8) and these as a model of adverse genetic conditions for brain development, we determined the effect of EE by raising these mice during early life under favorable conditions. We found a better generalized performance of SAMP8 under EE in the results of four behavioral and learning tests. In addition, we demonstrated broad molecular correlation in the hippocampus by an increase in NeuN and Ki67 expression, as well as an increase in the expression of neurotrophic factors, such as pleiotrophin (PTN) and brain-derived neurotrophic factor (BDNF), with a parallel decrease in neurodegenerative markers such as GSK3, amyloid-beta precursor protein, and phosphorylated beta-catenin, and a reduction of SBDP120, Bax, GFAP, and interleukin-6 (IL-6), resulting in a neuroprotective panorama. Globally, it can be concluded that EE applied to SAMP8 at young ages resulted in epigenetic regulatory mechanisms that give rise to significant beneficial effects at the molecular, cellular, and behavioral levels during brain development, particularly in the hippocampus.

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Acknowledgments

We thank Maggie Brunner, M.A., for revising the language and style of the manuscript. This study was supported by grant SAF-2012-39852 from the Spanish MINECO, and the European Regional Development Fund (SAF-2012-39852). CGF, VPA, AC, and MP belong to 2014SGR 525.

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Authors and Affiliations

  1. Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section) and Institute of Biomedicine (IBUB), Universitat de Barcelona, Avda. Joan XXIII s/n., 08028, Barcelona, Spain

    Christian Griñan-Ferré, Sofía Martínez Gutiérrez-Zetina, Antoni Camins, Verónica Palomera-Avalos & M. Pallàs

  2. Animal Experimentation Unit, Faculty of Pharmacy, University of Barcelona, Avda Joan XXIII s/n., 08028, Barcelona, Spain

    David Pérez-Cáceres & M. Teresa Rodrigo

  3. Instituto de Investigación en Ciencias Biomédicas (IICB), CUCS, Universidad de Guadalajara, Sierra Mojada No. 950, Col. Independencia, Guadalajara, 44340, Jalisco, Mexico

    Daniel Ortuño-Sahagún

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  1. Christian Griñan-Ferré
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Correspondence to M. Pallàs.

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Griñan-Ferré, C., Pérez-Cáceres, D., Gutiérrez-Zetina, S.M. et al. Environmental Enrichment Improves Behavior, Cognition, and Brain Functional Markers in Young Senescence-Accelerated Prone Mice (SAMP8). Mol Neurobiol 53, 2435–2450 (2016). https://doi.org/10.1007/s12035-015-9210-6

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