The Protective Effect Of Orally Long-term Administration Of Acarbose On The Impairment Of Spatial Learning And Memory In The Aged SAMP8 Mice

Background Age-associated memory impairment(AAMI) not only reduces the quality of life for the elderly but also increases the costs of healthcare for the society, therefore, it is of great importance to explore the methods that can alleviate the AAMI. Glucose metabolism and insulin / insulin-like growth factor 1(IGF-1) system are associated with the cognition. Impaired glucose metabolism and insulin / IGF-1 system will reduce the cognitive function, and enhanced glucose metabolism and insulin / IGF-1 system can improve the cognition. Acarbose, an inhibitor of a-glucosidase, not only can regulate the metabolism of glucose and the insulin / IGF-1 system, but also to delay the development and progress of age-related diseases, such as cardiovascular disease. Accordingly, we hypothesize that long-term oral administration of acarbose is able to ameliorate the progress of AAMI. Acetylated histone H3 lysine 9(H3K9ac) and acetylated histone H4 lysine 8(H4K8ac), the most well-researched facets of histone acetylation modification, are also related to the cognition. However, whether there is a relationship among H3K9 ac, H4K8 ac, acarbose and AAMI has not yet been reported.Objective Here, we used SAMP8 mice, the excellent animal model of aging and AAMI, to study the inhibitory effect of long-term oral administration of acarbose on AAMI, and explore whether blood glucose, insulin/IGF-1 system, H3K9 ac and H4K8 ac are associated with the potential effects.Methods 3-month old SAMP8 mice were randomly divided into the acarbose-treatment group(Aca, female 5, male 4) and the old blank control group(O-con, female 4, male 4). The treatment group received acarbose(20 mg/kg/d, dissolved in drinking water) at the age of 3-month until 9-month old before the behavioral test, and the controls only received water. Adding another group of 3-month old SAMP8 mice as the young blank control group(Y-con, female 6, male 5) and completed all tests with the other two groups of mice. Morris water maze test was used to detect the spatial learning and memory ability. Enzyme-linked immunosorbent assay and the immunohistochemical staining were respectively used to detect the blood parameters and the relative levels of hippocampal proteins.Results Compared to the Y-con, the O-con had significantly declined abilities of spatial learning and memory and levels of serum insulin, hippocampal insulin receptors(Ins Rs), H3K9 ac and H4K8 ac. Interestingly, the Aca group showed better abilities of spatial learning and memory and higher levels of insulin, Ins Rs, H3K9 ac and H4K8 ac relative to the O-con. Good performance of spatial learning and memory was positively correlated with the elevated levels of serum insulin and hippocampal Ins Rs, H3K9 ac and H4K8 ac.Conclusion Orally long-term administration of acarbose could alleviate the age-related impairment of spatial learning and memory in the SAMP8 mice, and the alleviated reduction of insulin system and H4K8 ac might be associated with the alleviation of learning and memory ability.