title: Chronic adjunction of 1-deoxynojirimycin protects from age-related behavioral and biochemical changes in the SAMP8 mice.
abstract: Several studies have indicated that a caloric restriction mimetic or treatment for type 2 diabetes may reverse brain aging. Therefore, we investigated the effect of 1-deoxynojirimycin (DNJ), an alkaloid acting as an inhibitor of α-glucosidase, on age-related behavioral and biochemical changes. SAMP8 mice were randomly assigned to a control group labeled "old" or to the 10- or 20-mg/kg/day DNJ groups. The mice in the DNJ groups were administered DNJ orally from 3 to 9 months of age, and then, a "young" control group was added to analyze the age effect. The old controls exhibited significant declines in sensorimotor ability, open-field anxiety, spatial and nonspatial memory abilities, and age-related biochemical changes, including decreased serum insulin level; increased levels of insulin-like growth factor 1 receptor, presynaptic protein synaptotagmin-1, and astrocyte activation; and decreased levels of insulin receptor, brain-derived neurotrophic factor, presynaptic protein syntaxin-1, and acetylation of histones H4 at lysine 8 in the dorsal hippocampus. Significant correlations exist between the age-related behavioral deficits and the serological and histochemical data. Chronic DNJ treatment alleviated these age-related changes, and the 20-mg/kg/day DNJ group showed more significant improvement. Thus, DNJ may have the potential to maintain successful brain aging.
authors.affiliation: Department of Neurology, the Affiliated Chaohu Hospital of Anhui Medical University, Chaohu, Hefei, 238000, People's Republic of China. doctorcgh@163.com.|School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, 230009, Anhui, People's Republic of China. doctorcgh@163.com.|Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People's Republic of China. doctorcgh@163.com.
authors.forename: Gui-Hai
authors.initials: GH
authors.lastname: Chen
authors.affiliation: Department of Rheumatism and Immunity, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People's Republic of China.|Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People's Republic of China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Tong
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, 230009, Anhui, People's Republic of China.
authors.forename: Xue-Qin
authors.initials: XQ
authors.lastname: Hu
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People's Republic of China.
authors.forename: Xue-Wei
authors.initials: XW
authors.lastname: Li
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Tao
authors.affiliation: School of Biotechnology and Food Engineering, Hefei University of Technology, Hefei, 230009, Anhui, People's Republic of China. zjwei@hfut.edu.cn.
authors.forename: Zhao-Jun
authors.initials: ZJ
authors.lastname: Wei
mesh_terms: D017485:1-Deoxynojirimycin / Q000008:administration & dosage*; D000284:Administration, Oral; D000375:Aging / Q000187:drug effects*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003071:Cognition / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051379:Mice
chemical_list: D004791:Enzyme Inhibitors; D017485:1-Deoxynojirimycin
keywords: 1-Deoxynojirimycin; BDNF; Brain aging; Histone acetylation; Insulin receptor; Learning and memory