title: Running exercise delays neurodegeneration in amygdala and hippocampus of Alzheimer's disease (APP/PS1) transgenic mice.
abstract: Alzheimer's disease (AD) is an age-related neurodegenerative disease. Post-mortem examination and brain imaging studies indicate that neurodegeneration is evident in the hippocampus and amygdala of very early stage AD patients. Exercise training is known to enhance hippocampus- and amygdala-associated neuronal function. Here, we investigated the effects of exercise (running) on the neuronal structure and function of the hippocampus and amygdala in APP/PS1 transgenic (Tg) mice. At 4-months-old, an age before amyloid deposition, the amygdala-associated, but not the hippocampus-associated, long-term memory was impaired in the Tg mice. The dendritic complexities of the amygdalar basolateral neurons, but not those in the hippocampal CA1 and CA3 neurons, were reduced. Furthermore, the levels of BDNF/TrkB signaling molecules (i.e. p-TrkB, p-Akt and p-PKC) were reduced in the amygdala, but not in the hippocampus of the 4-month-old Tg mice. The concentrations of Aβ40 and Aβ42 in the amygdala were higher than those in the hippocampus. Ten weeks of treadmill training (from 1.5- to 4-month-old) increased the hippocampus-associated memory and dendritic arbor of the CA1 and CA3 neurons, and also restored the amygdala-associated memory and the dendritic arbor of amygdalar basolateral neurons in the Tg mice. Similarly, exercise training also increased the levels of p-TrkB, p-AKT and p-PKC in the hippocampus and amygdala. Furthermore, exercise training reduced the levels of soluble Aβ in the amygdala and hippocampus. Exercise training did not change the levels of APP or RAGE, but significantly increased the levels of LRP-1 in both brain regions of the Tg mice. In conclusion, our results suggest that tests of amygdala function should be incorporated into subject selection for early prevention trials. Long-term exercise protects neurons in the amygdala and hippocampus against AD-related degeneration, probably via enhancements of BDNF signaling pathways and Aβ clearance. Physical exercise may serve as a means to delay the onset of AD.
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Tzu-Wei
authors.initials: TW
authors.lastname: Lin
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yao-Hsiang
authors.initials: YH
authors.lastname: Shih
authors.affiliation: Department of Engineering Science, National Cheng Kung University, Tainan 701, Taiwan; Advanced Optoelectronic Technology Center, National Cheng Kung University, Tainan 701, Taiwan; Center for Micro/Nano Science and Technology, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Shean-Jen
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Department of Engineering Science, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Chi-Hsiang
authors.initials: CH
authors.lastname: Lien
authors.affiliation: Department of Engineering Science, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Chia-Yuan
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Department of Physiology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Tung-Yi
authors.initials: TY
authors.lastname: Huang
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan; Department of Microbiology and Immunology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Shun-Hua
authors.initials: SH
authors.lastname: Chen
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan; Department of Physiology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chauying J
authors.initials: CJ
authors.lastname: Jen
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan; Department of Cell Biology and Anatomy, National Cheng Kung University, Tainan, Taiwan. Electronic address: kuoym@mail.ncku.edu.tw.
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Kuo
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D000679:Amygdala / Q000378:metabolism / Q000648:ultrastructure*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003214:Conditioning, Classical / Q000502:physiology; D003712:Dendrites / Q000648:ultrastructure; D004195:Disease Models, Animal; D005081:Exercise Therapy; D005239:Fear / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism / Q000648:ultrastructure*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure*; D010766:Phosphorylation; D053764:Presenilin-1 / Q000235:genetics; D020813:Receptor, trkB / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D019208:Brain-Derived Neurotrophic Factor; C508853:PSEN1 protein, human; D053764:Presenilin-1; D020813:Receptor, trkB
keywords: Alzheimer’s disease; Amygdala; Exercise; Hippocampus; Learning and memory; Neuroplasticity