title: ABCA1 Deficiency Affects Basal Cognitive Deficits and Dendritic Density in Mice.
abstract: ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol efflux to lipid-free apolipoproteins and regulates the generation of high density lipoproteins. Previously, we have shown that lack of Abca1 significantly increases amyloid deposition and cognitive deficits in Alzheimer's disease model mice expressing human amyloid-β protein precursor (APP). The goal of this study was to determine if ABCA1 plays a role in memory deficits caused by amyloid-β (Aβ) oligomers and examine neurite architecture of pyramidal hippocampal neurons. Our results confirm previous findings that Abca1 deficiency significantly impairs spatial memory acquisition and retention in the Morris water maze and long-term memory in novel object recognition of APP transgenic mice at a stage of early amyloid pathology. Neither test demonstrated a significant difference between Abca1ko and wild-type (WT) mice. We also examined the effect of intra-hippocampal infused Aβ oligomers on cognitive performance of Abca1ko mice, compared to control infusion of scrambled Aβ peptide. Age-matched WT mice undergoing the same infusions were also used as controls. In this model system, we found a statistically significant difference between WT and Abca1ko mice infused with scrambled Aβ, suggesting that Abca1ko mice are vulnerable to the effect of mild stresses. Moreover, examination of neurite architecture in the hippocampi revealed a significant decrease in neurite length, number of neurite segments, and branches in Abca1ko mice when compared to WT mice. We conclude that mice lacking ABCA1 have basal cognitive deficits that prevent them from coping with additional stressors, which is in part due to impairment of neurite morphology in the hippocampus.
authors.affiliation: Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Nicholas F
authors.initials: NF
authors.lastname: Fitz
authors.affiliation: Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Alexis Y
authors.initials: AY
authors.lastname: Carter
authors.affiliation: Department of Neurology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Tapias
authors.affiliation: Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Emilie L
authors.initials: EL
authors.lastname: Castranio
authors.affiliation: Department of Structural Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Ravindra
authors.initials: R
authors.lastname: Kodali
authors.affiliation: Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Iliya
authors.initials: I
authors.lastname: Lefterov
authors.affiliation: Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Radosveta
authors.initials: R
authors.lastname: Koldamova
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000172:deficiency* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D048429:Cell Size; D003072:Cognition Disorders / Q000378:metabolism* / Q000473:pathology*; D003712:Dendrites / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D021641:Recognition, Psychology / Q000502:physiology; D065852:Spatial Memory / Q000502:physiology
chemical_list: D064286:ATP Binding Cassette Transporter 1; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; C577833:Abca1 protein, mouse; C545487:APP protein, human; C508853:PSEN1 protein, human
keywords: APP mice; ATP-binding cassette transporter A1 (Abca1); Alzheimer’s disease; amyloid-β oligomers; behavior; hippocampal infusion; neurite morphology; radial arm water maze