title: Environmental enrichment lessens cognitive decline in APP23 mice without affecting brain sirtuin expression.
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-β (Aβ) 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 Aβ 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 AβPP expression or processing, Aβ40/42, pGlu-Aβ3-40/3-42, or Aβ oligomer level. The expression of two Aβ 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. Aβ 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 Aβ accumulation, but brain sirtuin expression was not modulated when cognitive impairment was restored.
authors: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy Golgi Cenci Foundation, Abbiategrasso, Italy.
authors: Letizia
authors: L
authors: Polito
authors: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors: Armando
authors: A
authors: Chierchia
authors: Department of Chemistry, Materials and Chemical Engineering "G. Natta", Politecnico di Milano and Unità di Ricerca Consorzio INSTM, Politecnico di Milano, Milan, Italy.
authors: Marta
authors: M
authors: Tunesi
authors: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors: Ihssane
authors: I
authors: Bouybayoune
authors: Dementia Research Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Frenchay Hospital, Bristol, UK.
authors: Patrick Gavin
authors: PG
authors: Kehoe
authors: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors: Diego
authors: D
authors: Albani
authors: IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors: Gianluigi
authors: G
authors: Forloni
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D039481:CD11b Antigen / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology / Q000451:nursing / Q000473:pathology; D004195:Disease Models, Animal; D004777:Environment; D005106:Exploratory Behavior / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: APP23 mice; Alzheimer's disease; cognitive impairment; environmental enrichment; sirtuin