title: LDL receptor knock-out mice show impaired spatial cognition with hippocampal vulnerability to apoptosis and deficits in synapses.
abstract: BACKGROUND
  Evidence from clinical studies support the fact that abnormal cholesterol metabolism in the brain leads to progressive cognitive dysfunction. The low-density lipoprotein receptor (LDLR) is well-known for its role in regulating cholesterol metabolism. Whether LDLR involved in this impaired cognition and the potential mechanisms that underlie this impairment are unknown.
  
  
  METHODS
  Twelve-month-old Ldlr-/- mice (n = 10) and wild-type littermates C57BL/6 J (n = 14) were subjected to the Morris water maze test. At 1 week after completion of the behavioural testing, all of the animals were sacrificed for analysis of synaptic and apoptotic markers.
  
  
  RESULTS
  The plasma cholesterol concentration of Ldlr-/- mice was increased moderately when compared with C57BL/6 J mice (P < 0.05). Behavioural testing revealed that Ldlr-/- mice displayed impaired spatial memory, and moreover, the expression levels of synaptophysin and the number of synaptophysin-immunoreactive presynaptic boutons in the hippocampal CA1 and dentate gyrus were decreased (all P < 0.05). Ultrastructural changes in the dentate gyrus were observed using transmission electron microscopy. Furthermore, apoptosis in the hippocampus of Ldlr-/- mice was revealed based on elevation, at both the mRNA and protein levels, of the ratio of Bax/Bcl-2 expression (all P < 0.05)and an increase in activated-caspase3 protein level (P < 0.05).
  
  
  CONCLUSIONS
  LDLR deficiency contributes to impaired spatial cognition. This most likely occurs via negative effects that promote apoptosis and synaptic deficits in the hippocampus.
authors.affiliation: Department of Endocrinology, ZhongDa Hospital of Southeast University, No,87 DingJiaQiao Road, Nanjing 210009, PR China. gyjwsh@126.com.
authors.forename: Shao-hua
authors.initials: SH
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yuan
authors.forename: Wen-qing
authors.initials: WQ
authors.lastname: Xia
authors.forename: Pin
authors.initials: P
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000378:metabolism* / Q000473:pathology; D003071:Cognition; D003072:Cognition Disorders / Q000235:genetics*; D015870:Gene Expression; D008297:Male; D018782:Maze Learning; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000235:genetics* / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000473:pathology
chemical_list: D051017:Apoptosis Regulatory Proteins; D011973:Receptors, LDL