Environmental enrichment induces neuroplastic changes in middle age female Balb/c mice and increases the hippocampal levels of BDNF, p-Akt and p-MAPK1/2

Neuroscience. 2014 Feb 28:260:158-70. doi: 10.1016/j.neuroscience.2013.12.026. Epub 2013 Dec 18.


Hippocampus is one of the brain regions in which neuroplastic changes occur. Paradigms such as environmental enrichment (ENR) have been used to prevent or delay the neuroplastic changes of the hippocampus during aging. Here, we investigated the beneficial effects of ENR on dendritic spines and hippocampal neurogenesis in middle age Balb/c mice. ENR increased the number of dendritic spines, cell survival, and intermediate stages of the hippocampal neurodevelopment process. Also, ENR alters the distribution of cells involved in the neurogenic process along the dorsal-ventral dentate gyrus. In addition, ENR increased the proportion of cells with more mature dendritic morphology and net hippocampal neurogenesis. Whole-hippocampus protein extracts revealed that ENR increases the levels of BDNF, phospho-Akt and phospho-MAPK1/2, suggesting that the positive effects of ENR on neuroplasticity in middle age Balb/c mice involve the participation of these key-signaling proteins. Our results suggest that ENR is a relevant strategy to prevent neuroplastic decline by increasing the formation of both dendritic spines and new neurons in the hippocampus during middle age.

Keywords: BDNF; CR; DCX; EDTA; ENR; GCL; NH; PI3K; TTBS; Tween 20-TBS; ZT; Zeitgeber time; aging; brain-derived neurotrophic factor; calretinin; doublecortin; environmental enrichment; ethylenediaminetetraacetic acid; granular cell layer; hippocampus; neurogenesis; neuroplasticity; normal housing; phosphatidylinositol-3-kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Dendritic Spines / ultrastructure*
  • Doublecortin Protein
  • Environment*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Hippocampus / metabolism*
  • Hippocampus / ultrastructure*
  • Mice
  • Mice, Inbred BALB C
  • Neurogenesis / physiology*
  • Neuronal Plasticity*
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism


  • Brain-Derived Neurotrophic Factor
  • Dcx protein, mouse
  • Doublecortin Protein
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases