Mid-life environmental enrichment increases synaptic density in CA1 in a mouse model of Aβ-associated pathology and positively influences synaptic and cognitive health in healthy ageing

J Comp Neurol. 2017 Jun 1;525(8):1797-1810. doi: 10.1002/cne.24156. Epub 2017 Mar 14.

Abstract

Early-life cognitive enrichment may reduce the risk of experiencing cognitive deterioration and dementia in later-life. However, an intervention to prevent or delay dementia is likely to be taken up in mid to later-life. Hence, we investigated the effects of environmental enrichment in wildtype mice and in a mouse model of Aβ neuropathology (APPSWE /PS1dE9 ) from 6 months of age. After 6 months of housing in standard laboratory cages, APPSWE /PS1dE9 (n = 27) and healthy wildtype (n = 21) mice were randomly assigned to either enriched or standard housing. At 12 months of age, wildtype mice showed altered synaptic protein levels and relatively superior cognitive performance afforded by environmental enrichment. Environmental enrichment was not associated with alterations to Aβ plaque pathology in the neocortex or hippocampus of APPSWE /PS1dE9 mice. However, a significant increase in synaptophysin immunolabeled puncta in the hippocampal subregion, CA1, in APPSWE /PS1dE9 mice was detected, with no significant synaptic density changes observed in CA3, or the Fr2 region of the prefrontal cortex. Moreover, a significant increase in hippocampal BDNF was detected in APPSWE /PS1dE9 mice exposed to EE, however, no changes were detected in neocortex or between Wt animals. These results demonstrate that mid to later-life cognitive enrichment has the potential to promote synaptic and cognitive health in ageing, and to enhance compensatory capacity for synaptic connectivity in pathological ageing associated with Aβ deposition.

Keywords: Alzheimer's disease; Aβ; RRID: SCR_002865; RRID:AB_1860491; RRID:AB_2263126; RRID:AB_2278725; RRID:AB_262185; RRID:AB_303248; RRID:AB_476743; RRID:AB_570874; RRID:AB_630940; RRID:MGI_3665286; RRID:SCR_002668; RRID:SCR_003070; brain-derived neurotrophic factor; cognitive function; environmental enrichment; transgenic mouse.

MeSH terms

  • Aging / physiology*
  • Alzheimer Disease / complications
  • Alzheimer Disease / pathology*
  • Animals
  • Blotting, Western
  • CA1 Region, Hippocampal / pathology*
  • Cognition Disorders / etiology
  • Cognition Disorders / pathology
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Housing, Animal*
  • Image Processing, Computer-Assisted
  • Male
  • Maze Learning
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Random Allocation
  • Synapses / pathology*