Environmental Enrichment Lessens Cognitive Decline in APP23 Mice Without Affecting Brain Sirtuin Expression

Letizia Polito, Armando Chierchia, Marta Tunesi, Ihssane Bouybayoune, Patrick Gavin Kehoe, Diego Albani*, Gianluigi Forloni

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

21 Citations (Scopus)

Abstract

Environmental enrichment (EE) is a non-pharmacological intervention reported to counteract pathological signs in models of Alzheimer's disease (AD). We developed EE protocols in APP23 mice and evaluated how they influenced cognitive decline and brain amyloid-beta (A beta) burden. We also investigated the involvement of sirtuins (SIRTs) as a possible molecular mediator of EE, by assessing hippocampal and cortical mRNA and protein levels of the SIRT family members (SIRT1 to SIRT7). APP23 transgenic mice were moved to EE cages (TG-EEs) starting from 3 months of age. TG-EEs were compared to transgenic mice housed in standard cages (TG-SHs) and to wild-type littermates in the two housing conditions (WT-EEs and WT-SHs). At 7 months of age, all mice were tested for behavioral performance with Morris Water Maze (MWM) and visual novel Object Recognition Test (vORT). After a month, a group underwent biochemical analyses, while another group continued in the EE environment till 18 months of age, when A beta plaque load was assessed. At 7 months, TG-SHs had impaired behavioral performance in MWM and vORT. In contrast, TG-EE mice had restored behavioral performance. At 8 months, EE did not affect A beta PP expression or processing, A beta(40/42), pGlu-A beta(3-40/3-42), or A beta oligomer level. The expression of two A beta degrading enzymes (insulin degrading enzyme and neprilysin) was not modulated by EE. Brain sirtuin mRNA and protein levels were unchanged, while brain-derived neurotrophic factor expression increased after EE. A beta deposition was attenuated in 18-month-old TG-EE mice, without apparent reduction of neuroinflammatory signs. We suggest that EE had a beneficial effect on cognitive performance and lessened long-term A beta accumulation, but brain sirtuin expression was not modulated when cognitive impairment was restored.

Original languageEnglish
Pages (from-to)851-864
Number of pages14
JournalJournal of Alzheimer's Disease
Volume42
Issue number3
DOIs
Publication statusPublished - 24 Jun 2014

Keywords

  • Alzheimer's disease
  • APP23 mice
  • cognitive impairment
  • environmental enrichment
  • sirtuin
  • TRANSGENIC MOUSE MODELS
  • ALZHEIMERS-DISEASE
  • PHYSICAL-ACTIVITY
  • AMYLOID DEPOSITION
  • NEUROTROPHIC FACTOR
  • ENDURANCE EXERCISE
  • IMPROVES COGNITION
  • SKELETAL-MUSCLE
  • AGED RATS
  • BETA

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