title: Chronic Sleep Restriction Induces Cognitive Deficits and Cortical Beta-Amyloid Deposition in Mice via BACE1-Antisense Activation.
abstract: OBJECTIVE
  To clarify the correlation between chronic sleep restriction (CSR) and sporadic Alzheimer disease (AD), we determined in wild-type mice the impact of CSR, on cognitive performance, beta-amyloid (Aβ) peptides, and its feed-forward regulators regarding AD pathogenesis.
  
  
  METHODS
  Sixteen nine-month-old C57BL/6 male mice were equally divided into the CSR and control groups. CSR was achieved by application of a slowly rotating drum for 2 months. The Morris water maze test was used to assess cognitive impairment. The concentrations of Aβ peptides, amyloid precursor protein (APP) and β-secretase 1 (BACE1), and the mRNA levels of BACE1 and BACE1-antisense (BACE1-AS) were measured.
  
  
  RESULTS
  Following CSR, impairments of spatial learning and memory consolidation were observed in the mice, accompanied by Aβ plaque deposition and an increased Aβ concentration in the prefrontal and temporal lobe cortex. CSR also upregulated the β-secretase-induced cleavage of APP by increasing the protein and mRNA levels of BACE1, particularly the BACE1-AS.
  
  
  CONCLUSIONS
  This study shows that a CSR accelerates AD pathogenesis in wild-type mice. An upregulation of the BACE1 pathway appears to participate in both cortical Aβ plaque deposition and memory impairment caused by CSR. BACE1-AS is likely activated to initiate a cascade of events that lead to AD pathogenesis. Our study provides, therefore, a molecular mechanism that links CSR to sporadic AD.
authors.affiliation: Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Hong-Yi
authors.initials: HY
authors.lastname: Zhao
authors.affiliation: Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Wu
authors.affiliation: Academy of Clinical Medicine, Second Military Medical University, Shanghai, China.
authors.forename: Jia-Lin
authors.initials: JL
authors.lastname: He
authors.affiliation: Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Zhuang
authors.affiliation: Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Liu
authors.affiliation: Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Liu-Qing
authors.initials: LQ
authors.lastname: Huang
authors.affiliation: Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Zhong-Xin
authors.initials: ZX
authors.lastname: Zhao
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D003072:Cognition Disorders / Q000209:etiology*; D016373:DNA, Antisense / Q000494:pharmacology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects; D012892:Sleep Deprivation / Q000150:complications* / Q000473:pathology*; D065853:Spatial Learning / Q000502:physiology; D065852:Spatial Memory / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016373:DNA, Antisense; D012333:RNA, Messenger; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse
keywords: BACE1; BACE1-antisense; Beta-amyloid; Chronic sleep restriction; Sporadic Alzheimer disease