Chronic adjunction of 1-deoxynojirimycin protects from age-related behavioral and biochemical changes in the SAMP8 mice.

Publisher: Springer Country of Publication: Netherlands NLM ID: 101250497 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1574-4647 (Electronic) Linking ISSN: 01619152 NLM ISO Abbreviation: Age (Dordr) Subsets: MEDLINE

Original Publication: Dordrecht, The Netherlands ; Hingham, MA : Springer, c2005-

1-Deoxynojirimycin/*administration & dosage ; Aging/*drug effects ; Behavior, Animal/*physiology ; Brain/*metabolism ; Cognition/*drug effects ; Maze Learning/*drug effects; Administration, Oral ; Animals ; Brain/drug effects ; Dose-Response Relationship, Drug ; Enzyme Inhibitors/administration & dosage ; Female ; Male ; Mice

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.

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Keywords: 1-Deoxynojirimycin; BDNF; Brain aging; Histone acetylation; Insulin receptor; Learning and memory

0 (Enzyme Inhibitors)
19130-96-2 (1-Deoxynojirimycin)

Date Created: 20150925 Date Completed: 20160517 Latest Revision: 20181113

20221213

PMC5005858

10.1007/s11357-015-9839-0

26400487