title: CaMKII-dependent dendrite ramification and spine generation promote spatial training-induced memory improvement in a rat model of sporadic Alzheimer's disease.
abstract: Participation in cognitively stimulating activities can preserve memory capacities in patients with Alzheimer's disease (AD), but the mechanism is not fully understood. Here, we used a rat model with hyperhomocysteinemia, an independent risk factor of AD, to study whether spatial training could remodel the synaptic and/or dendritic plasticity and the key molecular target(s) involved. We found that spatial training in water maze remarkably improved the subsequent short-term and long-term memory performance in contextual fear conditioning and Barnes maze. The trained rats showed an enhanced dendrite ramification, spine generation and plasticity in dentate gyrus (DG) neurons, and stimulation of long-term potentiation between perforant path and DG circuit. Spatial training also increased the levels of postsynaptic GluA1, GluN2A, GluN2B, and PSD93 with selective activation of calcium/calmodulin-dependent protein kinase II (CaMKII), although inhibition of CaMKII by stereotaxic injection of KN93 into hippocampal DG, abolished the training-induced cognitive improvement, dendrite ramification, and spine generation. We conclude that spatial training can preserve the cognitive function by CaMKII-dependent remodeling of dendritic plasticity in hyperhomocysteinemia-induced sporadic AD-like rats.
authors.affiliation: Department of Pathophysiology, Key Laboratory of Ministry of Education for Neurological Disorders, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China; Department of Pathology, Hubei University of Chinese Medicine, Wuhan, Hubei Province, P. R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Pathophysiology, Key Laboratory of Ministry of Education for Neurological Disorders, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China; Department of Basic Medicine, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu Province, 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, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 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, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 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, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 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, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 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, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Key Laboratory of Ministry of Education for Neurological Disorders, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China. Electronic address: wangjz@mails.tjmu.edu.cn.
authors.forename: Jian-Zhi
authors.initials: JZ
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Key Laboratory of Ministry of Education for Neurological Disorders, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China. Electronic address: liugp111@mail.hust.edu.cn.
authors.forename: Gong-Ping
authors.initials: GP
authors.lastname: Liu
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000503:physiopathology* / Q000523:psychology* / Q000628:therapy; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000502:physiology*; D003071:Cognition / Q000502:physiology; D049229:Dendritic Spines / Q000502:physiology*; D004195:Disease Models, Animal; D017774:Long-Term Potentiation; D008297:Male; D008568:Memory / Q000502:physiology*; D058990:Molecular Targeted Therapy; D009416:Nerve Regeneration / Q000235:genetics* / Q000502:physiology*; D009473:Neuronal Plasticity / Q000235:genetics* / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D065854:Spatial Navigation / Q000502:physiology*
chemical_list: D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: Alzheimer's disease; Calcium/calmodulin-dependent protein kinase II; Dendrite ramification; Spatial memory; Spatial training; Spine generation