title: Age-independent and age-related deficits in visuospatial learning, sleep-wake states, thermoregulation and motor activity in PDAPP mice.
abstract: Recent studies demonstrated that mice overexpressing the human mutant beta-amyloid precursor protein (hbetaAPP; PDAPP mice) show age-independent and age-related deficits in spatial learning. We used behavioral and electrophysiological techniques to determine in young and aged PDAPP mice whether deficits in spatial learning also involve alterations in sleep-wake states, thermoregulation and motor activity. Consistent with earlier studies, young PDAPP mice exhibited selective age-independent deficits using spatial, but not random and serial strategies in the circular maze. Aged PDAPP mice exhibited deficits using all search strategies. The core body temperature (Tb) in young and aged PDAPP mice was significantly lower than in age-matched non-transgenic (non-Tg) littermates. During the dark period, the motor activity (LMA) was significantly increased in young PDAPP mice, but not in aged PDAPP mice. During the light period, young PDAPP mice showed a reduction in the generation of rapid-eye-movement (REM) sleep. In contrast, aged PDAPP mice exhibited a reduction in the amount of time spent in W and an increase in SWS during the light period. Aged PDAPP mice also showed an increase in the amount of time spent in W and a reduction in REM sleep during the dark period. Our findings support previous reports indicating deficits in spatial learning in young and aged PDAPP mice. These data also suggest that PDAPP mice exhibit age-independent and age-related deficits in neural mechanisms regulating visuospatial learning, the total amount and the circadian distribution of sleep-wake states, thermoregulation and motor activity.
authors.affiliation: Department of Neuropharmacology, CVN-13, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037, USA.
authors.forename: Salvador
authors.initials: S
authors.lastname: Huitrón-Reséndiz
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez-Alavez
authors.forename: Roger
authors.initials: R
authors.lastname: Gallegos
authors.forename: Greta
authors.initials: G
authors.lastname: Berg
authors.forename: Elena
authors.initials: E
authors.lastname: Crawford
authors.forename: Jeannie L
authors.initials: JL
authors.lastname: Giacchino
authors.forename: Dora
authors.initials: D
authors.lastname: Games
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Henriksen
authors.forename: José R
authors.initials: JR
authors.lastname: Criado
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001833:Body Temperature Regulation / Q000235:genetics; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D021081:Chronobiology Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D012893:Sleep Wake Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D016564:Amyloid beta-Protein Precursor