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Environmental enrichment inhibits spontaneous apoptosis, prevents seizures and is neuroprotective

Abstract

The mammalian brain has a high degree of plasticity, with dentate granule cell neurogenesis1 and glial2,3 proliferation stimulated by an enriched environment combining both complex inanimate and social stimulation. Moreover, rodents exposed to an enriched environment both before and after a cerebral insult show improved cognitive performance1,4. One of the most robust associations of environmental enrichment is improved learning and memory in the Morris water maze, a spatial task that mainly involves the hippocampus5. Furthermore, clinical evidence showing an association between higher educational attainment and reduced risk of Alzheimer6 and Parkinson-related dementia7 indicates that a stimulating environment has positive effects on cerebral health that may provide some resilience to cerebral insults. Here we show that in addition to its effects on neurogenesis, an enriched environment reduces spontaneous apoptotic cell death in the rat hippocampus by 45%. Moreover, these environmental conditions protect against kainate-induced seizures and excitotoxic injury. The enriched environment induces expression of glial-derived neurotrophic factor and brain-derived neurotrophic factor and increases phosphorylation of the transcription factor cyclic-AMP response element binding protein, indicating that the influence of the environment on spontaneous apoptosis and cerebral resistance to insults may be mediated through transcription factor activation and induction of growth factor expression.

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Figure 1: Increased neurogenesis and reduced spontaneous apoptosis after environmental enrichment.
Figure 2: Seizure-induced neuronal injury in the hippocampus.
Figure 3: Growth factor increases after enrichment.

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Acknowledgements

We thank S. McPhee for providing assistance with Adobe Photoshop. This work was supported by grants from the New Zealand Health Research Council, Marsden Fund, New Zealand Neurological Foundation and Jefferson Faculty Foundation.

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Correspondence to Matthew J. During.

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Young, D., Lawlor, P., Leone, P. et al. Environmental enrichment inhibits spontaneous apoptosis, prevents seizures and is neuroprotective. Nat Med 5, 448–453 (1999). https://doi.org/10.1038/7449

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