Environmental enrichment inhibits spontaneous apoptosis, prevents seizures and is neuroprotective

Nat Med. 1999 Apr;5(4):448-53. doi: 10.1038/7449.


The mammalian brain has a high degree of plasticity, with dentate granule cell neurogenesis and glial 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 performance. 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 hippocampus. Furthermore, clinical evidence showing an association between higher educational attainment and reduced risk of Alzheimer and Parkinson-related dementia 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Brain-Derived Neurotrophic Factor / biosynthesis
  • Brain-Derived Neurotrophic Factor / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Dentate Gyrus / growth & development
  • Dentate Gyrus / pathology
  • Environment*
  • Glial Cell Line-Derived Neurotrophic Factor
  • Hippocampus / growth & development
  • Hippocampus / pathology*
  • In Situ Hybridization
  • Kainic Acid / adverse effects*
  • Male
  • Nerve Growth Factors*
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Phosphorylation
  • RNA, Messenger / isolation & purification
  • Rats
  • Rats, Wistar
  • Seizures / chemically induced
  • Seizures / prevention & control*


  • Brain-Derived Neurotrophic Factor
  • Cyclic AMP Response Element-Binding Protein
  • Gdnf protein, rat
  • Glial Cell Line-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Kainic Acid