title: Manipulation of caloric content but not diet composition, attenuates the deficit in learning and memory of senescence-accelerated mouse strain P8.
abstract: Calorie restriction (CR) is an experimental intervention in laboratory animals that attenuates age-associated increases in morbidity, mortality, and functional impairment. It is characterized by mild ketosis, hypoinsulinemia and hypoglycemia. In this study, we examined whether metabolic simulation of CR by a diet of isocaloric ketogenic or hypoinsulinemic diets ameliorated the learning and memory deficit in a strain of senescence-accelerated prone mice (SAMP8), a mouse model of age-dependent impairments in learning and memory. Male SAMP8 mice were fed high carbohydrate (CHO), high fat (FAT), or high protein (PRO) diets after weaning, and calorie intake was adjusted to 95% (sub ad libitum, sAL) or 70% (CR) of the mean calorie intake of control mice. At 28 weeks of age, we found CR ameliorated the performance defects of SAMP8 mice in a passive avoidance task. Neither FAT nor PRO diets affected performance of the task when fed sAL level, although a diet of these compositions partially mimicked the serum parameters of CR mice. These results suggest restriction of calorie intake is important for the prevention of learning and memory deficits, and that the simulation of serum changes induced by CR is not sufficient to prevent the cognitive defects of SAMP8 mice.
authors.affiliation: Department of Investigative Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Nagasaki, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Komatsu
authors.forename: Takuya
authors.initials: T
authors.lastname: Chiba
authors.forename: Haruyoshi
authors.initials: H
authors.lastname: Yamaza
authors.forename: Kimihiro
authors.initials: K
authors.lastname: Yamashita
authors.forename: Atsuyoshi
authors.initials: A
authors.lastname: Shimada
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Hoshiyama
authors.forename: Tomoko
authors.initials: T
authors.lastname: Henmi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohtani
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Higami
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cabo
authors.forename: Donald K
authors.initials: DK
authors.lastname: Ingram
authors.forename: Isao
authors.initials: I
authors.lastname: Shimokawa
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D001921:Brain / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis; D031204:Caloric Restriction; D016022:Case-Control Studies; D004032:Diet; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008569:Memory Disorders / Q000503:physiopathology*; D051379:Mice; D008815:Mice, Inbred Strains; D018384:Oxidative Stress
chemical_list: D001786:Blood Glucose; D019208:Brain-Derived Neurotrophic Factor; D008315:Malondialdehyde