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.

Accelerated reduction of serum thyroxine and hippocampal histone acetylation links to exacerbation of spatial memory impairment in aged CD-1 mice pubertally exposed to bisphenol-a

“…In another study by Intlekofer et al (2013), the effect of exercise and NaB on transforming a subthreshold learning event into longterm memory is associated with increased H4K8ac of brain-derived neurotrophic factor promoter. Our recent studies also find that chronically oral administration of acarbose and 1-deoxynojirimycin can alleviate the agerelated impairment of SLM and the alleviation tended to be associated with alleviated reduction of H4K8ac (Chen et al 2015;Yan et al 2015). Taken together, existing findings suggest that accelerating the reduction of H3K9ac and H4K8ac may be associated with the effect of pubertal BPA exposure on accelerating agerelated decline in SLM.…”

Effects of Embryonic Inflammation and Adolescent Psychosocial Environment on Cognition and Hippocampal Staufen in Middle-Aged Mice

“…The time it takes for mice to reach the escape platform (escape latency) is the most commonly used measure of learning performance; however, escape latency can be affected by swimming speed, which usually declines with age ( van der Staay and de Jonge, 1993 ). Therefore, in this study, the total swimming distance in the learning phase was used as the spatial learning ability and the percent distance swam in the target quadrant in the probe test was used as the memory performance ( Chen et al, 2015 ; Zhang et al, 2020 ). ANY-maze software (Stöelting, United States) was used to record the distance swam.…”

Physiological Effects and Organ Distribution of <i>Bacillus amyloliquefaciens</i> AS385 Culture Broth Powder Containing 1-Deoxynojirimycin in C57BL/6J Mice

“…In the meantime, only small information can be gained concerning the effect of dietary DNJ on brain region. One of the notable studies by Chen et al (51) has shown the amelioration of the age-related behavioral decline in SAMP8 mice after long-term DNJ supplementation in drinking water (10 and 20 mg/kg body weight/d). While this study linked the elevation of hippocampal insulin receptor level after DNJ intake with the improvement of brain degeneration, the underlying mechanism for this alteration has remained unknown.…”