title: Endoplasmic Reticulum Stress Induces the Early Appearance of Pro-apoptotic and Anti-apoptotic Proteins in Neurons of Five Familial Alzheimer's Disease Mice.
abstract: BACKGROUND
  Amyloid β (Aβ) deposits and the endoplasmic reticulum stress (ERS) are both well established in the development and progression of Alzheimer's disease (AD). However, the mechanism and role of Aβ-induced ERS in AD-associated pathological progression remain to be elucidated.
  
  
  METHODS
  The five familial AD (5×FAD) mice and wild-type (WT) mice aged 2, 7, and 12 months were used in the present study. Morris water maze test was used to evaluate their cognitive performance. Immunofluorescence and Western blot analyses were used to examine the dynamic changes of pro-apoptotic (CCAAT/enhancer-binding protein homologous protein [CHOP] and cleaved caspase-12) and anti-apoptotic factors (chaperone glucose-regulated protein [GRP] 78 and endoplasmic reticulum-associated protein degradation-associated ubiquitin ligase synovial apoptosis inhibitor 1 [SYVN1]) in the ERS-associated unfolded protein response (UPR) pathway.
  
  
  RESULTS
  Compared with age-matched WT mice, 5×FAD mice showed higher cleaved caspase-3, lower neuron-positive staining at the age of 12 months, but earlier cognitive deficit at the age of 7 months (all P < 0.05). Interestingly, for 2-month-old 5×FAD mice, the related proteins involved in the ERS-associated UPR pathway, including CHOP, cleaved caspase-12, GRP 78, and SYVN1, were significantly increased when compared with those in age-matched WT mice (all P < 0.05). Moreover, ERS occurred mainly in neurons, not in astrocytes.
  
  
  CONCLUSIONS
  These findings suggest that compared with those of age-matched WT mice, ERS-associated pro-apoptotic and anti-apoptotic proteins are upregulated in 2-month-old 5×FAD mice, consistent with intracellular Aβ aggregation in neurons.
authors.affiliation: Department of Neurology and Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital; Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Neurology and Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital; Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Pan
authors.affiliation: Department of Neurology and Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital; Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurology and Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital; Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China.
authors.forename: Yu-Qi
authors.initials: YQ
authors.lastname: Zeng
authors.affiliation: Department of Neurology and Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital; Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Neurology and Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital; Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China.
authors.forename: Lu-Meng
authors.initials: LM
authors.lastname: Yang
authors.affiliation: Department of Neurology and Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital; Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Ye
authors.affiliation: Department of Neurology and Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital; Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China.
authors.forename: Xiao-Man
authors.initials: XM
authors.lastname: Dai
authors.affiliation: Department of Neurology and Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital; Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China.
authors.forename: Yuan-Gui
authors.initials: YG
authors.lastname: Zhu
authors.affiliation: Department of Neurology and Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital; Key Laboratory of Brain Aging and Neurodegenerative Diseases, Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, Fujian 350001, China.
authors.forename: Xiao-Chun
authors.initials: XC
authors.lastname: Chen
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D053454:Caspase 12 / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D005625:Frontal Lobe / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D051742:Transcription Factor CHOP / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D056811:Unfolded Protein Response / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; C497250:Ddit3 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D051742:Transcription Factor CHOP; C498235:Syvn1 protein, mouse; D044767:Ubiquitin-Protein Ligases; D053454:Caspase 12