title: Aerobic exercise combined with antioxidative treatment does not counteract moderate- or mid-stage Alzheimer-like pathophysiology of APP/PS1 mice.
abstract: OBJECTIVE
  The present study evaluated the combined treatment effects of aerobic exercise and antioxidative stress on moderate-stage Alzheimer's disease (AD).
  
  
  METHODS
  Ten-month-old APP/PS1 mice were given antioxidative treatment with acetylcysteine, along with aerobic exercise for 6 weeks. Spatial learning and memory were tested using the Morris water maze, and β-amyloid (Aβ) plaque deposits in the forebrain were quantified by Thioflavin-S staining. Levels of soluble Aβ1-42, β-secretase enzyme, ү-secretase enzyme, oxidative and antioxidant stress markers nitrotyrosine and peroxiredoxin-1, glial markers glial fibrillary acidic protein and ionized calcium-binding adaptor molecule 1, and synaptic protein synaptophysin in the hippocampus were all measured by western blotting and/or immunohistochemistry.
  
  
  RESULTS
  APP/PS1 mice showed severe declines in spatial learning and memory compared with their wild-type littermates, which were not attenuated by aerobic exercise combined with antioxidative treatment. The pathologic analysis revealed that Aβ deposition and production, oxidative stress, glial inflammation, and synaptic loss were not mitigated in the brain of exercised APP/PS1 mice, compared with the sedentary APP/PS1 animals.
  
  
  CONCLUSIONS
  This study reveals that a combined treatment of aerobic exercise plus antioxidative stress does not counteract pathophysiology in the moderate- or mid-stages of AD.
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Xu
authors.forename: Lu-Qing
authors.initials: LQ
authors.lastname: Zhang
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Charles
authors.initials: C
authors.lastname: Marshall
authors.forename: Na
authors.initials: N
authors.lastname: Xiao
authors.forename: Jun-Ying
authors.initials: JY
authors.lastname: Gao
authors.forename: Ting
authors.initials: T
authors.lastname: Wu
authors.forename: Jiong
authors.initials: J
authors.lastname: Ding
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
authors.forename: Ming
authors.initials: M
authors.lastname: Xiao
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D007249:Inflammation / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D051379:Mice; D008822:Mice, Transgenic; D010805:Physical Conditioning, Animal / Q000379:methods* / Q000502:physiology; D053764:Presenilin-1 / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D016564:Amyloid beta-Protein Precursor; D000975:Antioxidants; D053764:Presenilin-1
keywords: APP/PS1 mice; Aerobic exercise; Alzheimer's disease; Antioxidative treatment; Cognitive function; Pathology; β-amyloid