title: Spatial learning and memory impairments are associated with increased neuronal activity in 5XFAD mouse as measured by manganese-enhanced magnetic resonance imaging.
abstract: Dysfunction of neuronal activity is a major and early contributor to cognitive impairment in Alzheimer's disease (AD). To investigate neuronal activity alterations at early stage of AD, we encompassed behavioral testing and in vivo manganese-enhanced magnetic resonance imaging (MEMRI) in 5XFAD mice at early ages (1-, 2-, 3- and 5-month). The 5XFAD model over-express human amyloid precursor protein (APP) and presenilin 1 (PS1) harboring five familial AD mutations, which have a high APP expression correlating with a high burden and an accelerated accumulation of the 42 amino acid species of amyloid-β. In the Morris water maze, 5XFAD mice showed longer escape latency and poorer memory retention. In the MEMRI, 5XFAD mice showed increased signal intensity in the brain regions involved in spatial cognition, including the entorhinal cortex, the hippocampus, the retrosplenial cortex and the caudate putamen. Of note, the observed alterations in spatial cognition were associated with increased MEMRI signal intensity. These findings indicate that aberrant increased basal neuronal activity may contribute to the spatial cognitive function impairment at early stage of AD, and may further suggest the potential use of MEMRI to predict cognitive impairments. Early intervention that targets aberrant neuronal activity may be crucial to prevent cognitive impairment.
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Gu
authors.affiliation: Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Bin-Bin
authors.initials: BB
authors.lastname: Nie
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Xin-Yang
authors.initials: XY
authors.lastname: Qi
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Yan-Juan
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Wu
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Li
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Bai
authors.affiliation: Department of Neurology and Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
authors.forename: Xiao-Chun
authors.initials: XC
authors.lastname: Chen
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China.|Graduate School of Chinese Academy of Sciences, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Qing-Guo
authors.initials: QG
authors.lastname: Ren
authors.affiliation: Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Zhang
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D001931:Brain Mapping; D004195:Disease Models, Animal; D006801:Humans; D008279:Magnetic Resonance Imaging; D008345:Manganese; D018782:Maze Learning; D008569:Memory Disorders / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism*; D065853:Spatial Learning
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1; D008345:Manganese
keywords: 5XFAD mice; Alzheimer’s disease; Pathology Section; cognition; manganese enhanced MRI; neuroimaging