title: Long-term acarbose administration alleviating the impairment of spatial learning and memory in the SAMP8 mice was associated with alleviated reduction of insulin system and acetylated H4K8.
abstract: Age-associated memory impairment (AAMI) not only reduces the quality of life for the elderly but also increases the costs of healthcare for society. Methods that can regulate glucose metabolism, insulin/insulin-like growth factor 1 (IGF-1) system and acetylated histone H4 lysine 8 (H4K8ac), one of the most well-researched facets of histone acetylation modification associating with cognition, tend to ameliorate the AAMI. Here, we used SAMP8 mice, the excellent animal model of aging and AAMI, to study the effect of long-term treatment with acarbose, an inhibitor of a-glucosidase, on AAMI and explore whether blood glucose, insulin/IGF-1 system and H4K8ac are associated with potential effects. The treatment group received acarbose (20mg/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. Compared to the young controls (3-month-old, n=11), the old group (9-month-old, n=8) had declined abilities of spatial learning and memory and levels of serum insulin, hippocampal insulin receptors (InsRs) and H4K8ac. Interestingly, the acarbose group (9-month-old, n=9) showed better abilities of spatial learning and memory and higher levels of insulin, InsRs and H4K8ac relative to the old controls. Good performance of spatial learning and memory was positively correlated with the elevated insulin, InsRs and H4K8ac. All these results suggested that 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 an insulin system and H4K8ac might be associated with the alleviation.
authors: Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, PR China.
authors: Wen-Wen
authors: WW
authors: Yan
authors: Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, PR China; Department of Neurology, The First People׳s Hospital of Chenzhou, Southern Medical University, Chenzhou 423000, Hunan Province, PR China. Electronic address: doctorcgh@163.com.
authors: Gui-Hai
authors: GH
authors: Chen
authors: Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, PR China.
authors: Fang
authors: F
authors: Wang
authors: Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, PR China.
authors: Jing-Jing
authors: JJ
authors: Tong
authors: Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, PR China.
authors: Fei
authors: F
authors: Tao
mesh_terms: D020909:Acarbose / Q000494:pharmacology*; D000375:Aging / Q000187:drug effects / Q000378:metabolism / Q000523:psychology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D006657:Histones / Q000378:metabolism*; D007328:Insulin / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy* / Q000503:physiopathology; D051379:Mice; D018697:Nootropic Agents / Q000494:pharmacology*; D011897:Random Allocation; D011972:Receptor, Insulin / Q000378:metabolism; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D006657:Histones; D007328:Insulin; D018697:Nootropic Agents; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin; D020909:Acarbose
keywords: Acarbose; Acetylated histone; Aging; Insulin system; Learning; Memory