title: Repeated cognitive stimulation alleviates memory impairments in an Alzheimer's disease mouse model.
abstract: Alzheimer's disease is a neurodegenerative disease associated with progressive memory and cognitive decline. Previous studies have identified the benefits of cognitive enrichment on reducing disease pathology. Additionally, epidemiological and clinical data suggest that repeated exercise, and cognitive and social enrichment, can improve and/or delay the cognitive deficiencies associated with aging and neurodegenerative diseases. In the present study, 3xTg-AD mice were exposed to a rigorous training routine beginning at 3 months of age, which consisted of repeated training in the Morris water maze spatial recognition task every 3 months, ending at 18 months of age. At the conclusion of the final Morris water maze training session, animals subsequently underwent testing in another hippocampus-dependent spatial task, the Barnes maze task, and on the more cortical-dependent novel object recognition memory task. Our data show that periodic cognitive enrichment throughout aging, via multiple learning episodes in the Morris water maze task, can improve the memory performance of aged 3xTg-AD mice in a separate spatial recognition task, and in a preference memory task, when compared to naïve aged matched 3xTg-AD mice. Furthermore, we observed that the cognitive enrichment properties of Morris water maze exposer, was detectable in repeatedly trained animals as early as 6 months of age. These findings suggest early repeated cognitive enrichment can mitigate the diverse cognitive deficits observed in Alzheimer's disease.
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, CA, USA; Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Mexico.
authors.forename: Hilda
authors.initials: H
authors.lastname: Martinez-Coria
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, CA, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Yeung
authors.affiliation: Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
authors.forename: Rahasson R
authors.initials: RR
authors.lastname: Ager
authors.affiliation: School of Natural Sciences, University of California, Merced, CA, USA.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Rodriguez-Ortiz
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, CA, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Baglietto-Vargas
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, CA, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA. Electronic address: laferla@uci.edu.
authors.forename: Frank M
authors.initials: FM
authors.lastname: LaFerla
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology* / Q000628:therapy*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015928:Cognitive Behavioral Therapy / Q000379:methods*; D004195:Disease Models, Animal; D006801:Humans; D018782:Maze Learning; D008568:Memory; D008569:Memory Disorders / Q000503:physiopathology* / Q000628:therapy*; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1
keywords: 3xTg-AD; Alzheimer’s disease; Cognitive stimulation; Hippocampus; Morris water maze; Repeated learning