title: Spatial training preserves associative memory capacity with augmentation of dendrite ramification and spine generation in Tg2576 mice.
abstract: Alzheimer's disease (AD) is the most common neurodegenerative disorder and there is currently no efficient cure for this devastating disease. Cognitive stimulation can delay memory loss during aging and in patients with mild cognitive impairment. In 3 × Tg-AD mice, training decreased the neuropathologies with transient amelioration of memory decline. However, the neurobiological mechanisms underlying the learning-improved memory capacity are poorly understood. Here, we found in Tg2576 mice spatial training in Morris water maze (MWM) remarkably improved the subsequent associative memory acquisition detected by contextual fear conditioning. We also found that spatial training enhanced long term potentiation, dendrite ramification and spine generation in hippocampal dentate gyrus (DG) and CA1 neurons at 24 h after the training. In the molecular level, the MWM training remarkably activated calcium/calmodulin-dependent protein kinase II (CaMKII) with elevation of glutamate AMPA receptor GluA1 subunit (GluA1), postsynaptic density protein 93 (PSD93) and postsynaptic density protein 95 (PSD95) in the hippocampus. Finally, the training also significantly ameliorated AD-like tau and amyloid pathologies. We conclude that spatial training in MWM preserves associative memory capacity in Tg2576 mice, and the mechanisms involve augmentation of dendrite ramification and spine generation in hippocampus.
authors.affiliation: 1] Department of Pathophysiology, Key Laboratory of Ministry of Education for Neurological Disorders, the School of Basal Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030. P. R. China [2] Department of Pathology, Hubei University of Chinese Medicine, Wuhan, 430065. P. R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Jiang
authors.affiliation: 1] Department of Pathophysiology, Key Laboratory of Ministry of Education for Neurological Disorders, the School of Basal Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030. P. R. China [2] Department of Basic Medicine, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu Province, 214122, P. R. China.
authors.forename: Gao-Shang
authors.initials: GS
authors.lastname: Chai
authors.affiliation: Department of Pathophysiology, Key Laboratory of Ministry of Education for Neurological Disorders, the School of Basal Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030. P. R. China.
authors.forename: Zhi-Hao
authors.initials: ZH
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Key Laboratory of Ministry of Education for Neurological Disorders, the School of Basal Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030. P. R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Pathophysiology, Key Laboratory of Ministry of Education for Neurological Disorders, the School of Basal Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030. P. R. China.
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Key Laboratory of Ministry of Education for Neurological Disorders, the School of Basal Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030. P. R. China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Ma
authors.affiliation: Department of Pathophysiology, Key Laboratory of Ministry of Education for Neurological Disorders, the School of Basal Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030. P. R. China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.affiliation: 1] Department of Pathophysiology, Key Laboratory of Ministry of Education for Neurological Disorders, the School of Basal Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030. P. R. China [2] Co-innovation Center of Neuroregeneration, Nantong University, Nantong, JS 226001, China.
authors.forename: Jian-Zhi
authors.initials: JZ
authors.lastname: Wang
authors.affiliation: 1] Department of Pathophysiology, Key Laboratory of Ministry of Education for Neurological Disorders, the School of Basal Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030. P. R. China [2] Co-innovation Center of Neuroregeneration, Nantong University, Nantong, JS 226001, China.
authors.forename: Gong-Ping
authors.initials: GP
authors.lastname: Liu
mesh_terms: D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D018891:Dentate Gyrus / Q000378:metabolism; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D017774:Long-Term Potentiation; D008565:Membrane Proteins / Q000378:metabolism; D008568:Memory; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity; D010766:Phosphorylation; D017966:Pyramidal Cells / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D065853:Spatial Learning; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D008565:Membrane Proteins; D018091:Receptors, AMPA; D016875:tau Proteins; C501447:Dlg4 protein, mouse
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