title: Isolation Housing Exacerbates Alzheimer's Disease-Like Pathophysiology in Aged APP/PS1 Mice.
abstract: BACKGROUND
  Alzheimer's disease is a neurodegenerative disease characterized by gradual declines in social, cognitive, and emotional functions, leading to a loss of expected social behavior. Social isolation has been shown to have adverse effects on individual development and growth as well as health and aging. Previous experiments have shown that social isolation causes an early onset of Alzheimer's disease-like phenotypes in young APP695/PS1-dE9 transgenic mice. However, the interactions between social isolation and Alzheimer's disease still remain unknown.
  
  
  METHODS
  Seventeen-month-old male APP695/PS1-dE9 transgenic mice were either singly housed or continued group housing for 3 months. Then, Alzheimer's disease-like pathophysiological changes were evaluated by using behavioral, biochemical, and pathological analyses.
  
  
  RESULTS
  Isolation housing further promoted cognitive dysfunction and Aβ plaque accumulation in the hippocampus of aged APP695/PS1-dE9 transgenic mice, associated with increased γ-secretase and decreased neprilysin expression. Furthermore, exacerbated hippocampal atrophy, synapse and myelin associated protein loss, and glial neuroinflammatory reactions were observed in the hippocampus of isolated aged APP695/PS1-dE9 transgenic mice.
  
  
  CONCLUSIONS
  The results demonstrate that social isolation exacerbates Alzheimer's disease-like pathophysiology in aged APP695/PS1-dE9 transgenic mice, highlighting the potential role of group life for delaying or counteracting the Alzheimer's disease process.
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, Jiangsu, China (Drs Huang MD, Wang MD, Cao Ms, Gao Ms, N. Xiao Ms, Hu MD, PhD, and M. Xiao MD, PhD); Department of Rehabilitation Sciences, University of Kentucky Center for Excellence in Rural Health, Hazard, KY (Dr Marshall PhD).
authors.forename: Huang
authors.initials: H
authors.lastname: Huang
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, Jiangsu, China (Drs Huang MD, Wang MD, Cao Ms, Gao Ms, N. Xiao Ms, Hu MD, PhD, and M. Xiao MD, PhD); Department of Rehabilitation Sciences, University of Kentucky Center for Excellence in Rural Health, Hazard, KY (Dr Marshall PhD).
authors.forename: Linmei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, Jiangsu, China (Drs Huang MD, Wang MD, Cao Ms, Gao Ms, N. Xiao Ms, Hu MD, PhD, and M. Xiao MD, PhD); Department of Rehabilitation Sciences, University of Kentucky Center for Excellence in Rural Health, Hazard, KY (Dr Marshall PhD).
authors.forename: Min
authors.initials: M
authors.lastname: Cao
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, Jiangsu, China (Drs Huang MD, Wang MD, Cao Ms, Gao Ms, N. Xiao Ms, Hu MD, PhD, and M. Xiao MD, PhD); Department of Rehabilitation Sciences, University of Kentucky Center for Excellence in Rural Health, Hazard, KY (Dr Marshall PhD).
authors.forename: Charles
authors.initials: C
authors.lastname: Marshall
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, Jiangsu, China (Drs Huang MD, Wang MD, Cao Ms, Gao Ms, N. Xiao Ms, Hu MD, PhD, and M. Xiao MD, PhD); Department of Rehabilitation Sciences, University of Kentucky Center for Excellence in Rural Health, Hazard, KY (Dr Marshall PhD).
authors.forename: Junying
authors.initials: J
authors.lastname: Gao
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, Jiangsu, China (Drs Huang MD, Wang MD, Cao Ms, Gao Ms, N. Xiao Ms, Hu MD, PhD, and M. Xiao MD, PhD); Department of Rehabilitation Sciences, University of Kentucky Center for Excellence in Rural Health, Hazard, KY (Dr Marshall PhD).
authors.forename: Na
authors.initials: N
authors.lastname: Xiao
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, Jiangsu, China (Drs Huang MD, Wang MD, Cao Ms, Gao Ms, N. Xiao Ms, Hu MD, PhD, and M. Xiao MD, PhD); Department of Rehabilitation Sciences, University of Kentucky Center for Excellence in Rural Health, Hazard, KY (Dr Marshall PhD).
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, Jiangsu, China (Drs Huang MD, Wang MD, Cao Ms, Gao Ms, N. Xiao Ms, Hu MD, PhD, and M. Xiao MD, PhD); Department of Rehabilitation Sciences, University of Kentucky Center for Excellence in Rural Health, Hazard, KY (Dr Marshall PhD). mingx@njmu.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Xiao
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology / Q000523:psychology*; D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001284:Atrophy / Q000473:pathology; D001522:Behavior, Animal; D003071:Cognition; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D007249:Inflammation / Q000473:pathology; D008124:Locomotion; D008297:Male; D018782:Maze Learning; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity; D009186:Myelin Sheath / Q000473:pathology; D015260:Neprilysin / Q000378:metabolism; D009457:Neuroglia / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology; D012934:Social Isolation / Q000523:psychology*; D013569:Synapses / Q000473:pathology
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D053829:Amyloid Precursor Protein Secretases; D015260:Neprilysin
keywords: APP/PS1 mice; Alzheimer’s disease; hippocampus; memory deficiency; social isolation; β-amyloid