Experience-dependent reduction of soluble β-amyloid oligomers and rescue of cognitive abilities in middle-age Ts65Dn mice, a model of Down syndrome.
Down syndrome (DS) is the most diffused genetic cause of intellectual disability and, after the age of forty, is invariantly associated with Alzheimer's disease (AD). In the last years, the prolongation of life expectancy in people with DS renders the need for intervention paradigms aimed at improving mental disability and counteracting AD pathology particularly urgent. At present, however, there are no effective therapeutic strategies for DS and concomitant AD in mid-life people. The most intensively studied mouse model of DS is the Ts65Dn line, which summarizes the main hallmarks of the DS phenotype, included severe learning and memory deficits and age-dependent AD-like pathology. Here we report for the first time that middle-age Ts65Dn mice display a marked increase in soluble Aβ oligomer levels in their hippocampus. Moreover, we found that long-term exposure to environmental enrichment (EE), a widely used paradigm that increases sensory-motor stimulation, reduces Aβ oligomers and rescues spatial memory abilities in trisomic mice. Our findings underscore the potential of EE procedures as a non-invasive paradigm for counteracting brain aging processes in DS subjects.
Neuroscience Institute, National Research Council (CNR), Pisa, Italy; NEUROFARBA, University of Florence, Florence, Italy.
Gabriele
G
Sansevero
Neuroscience Institute, National Research Council (CNR), Pisa, Italy.
Tatjana
T
Begenisic
Neuroscience Institute, National Research Council (CNR), Pisa, Italy.
Marco
M
Mainardi
Neuroscience Institute, National Research Council (CNR), Pisa, Italy. Electronic address: sale@in.cnr.it.
Alessandro
A
Sale
D000375:Aging; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use; D003072:Cognition Disorders / Q000209:etiology* / Q000628:therapy*; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000150:complications*; D004777:Environment; D006801:Humans; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology / Q000628:therapy; D051379:Mice; D008822:Mice, Transgenic; D060172:Morpholinos / Q000627:therapeutic use*; D015260:Neprilysin / Q000276:immunology; D018709:Statistics, Nonparametric; D013550:Swimming / Q000523:psychology; D013997:Time Factors
D016229:Amyloid beta-Peptides; D000906:Antibodies; D060172:Morpholinos; D015260:Neprilysin
Aging; Alzheimer’s disease; Down syndrome; Environmental enrichment; Intellectual disability; Ts65Dn mice; β-amyloid oligomers