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ABCA1 Deficiency Affects Basal Cognitive Deficits and Dendritic Density in Mice
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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
IOS Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5302049/ https://www.ncbi.nlm.nih.gov/pubmed/28106559 http://dx.doi.org/10.3233/JAD-161056 |
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author | Fitz, Nicholas F. Carter, Alexis Y. Tapias, Victor Castranio, Emilie L. Kodali, Ravindra Lefterov, Iliya Koldamova, Radosveta |
author_facet | Fitz, Nicholas F. Carter, Alexis Y. Tapias, Victor Castranio, Emilie L. Kodali, Ravindra Lefterov, Iliya Koldamova, Radosveta |
author_sort | Fitz, Nicholas F. |
collection | PubMed |
description | 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 Abca1(ko) and wild-type (WT) mice. We also examined the effect of intra-hippocampal infused Aβ oligomers on cognitive performance of Abca1(ko) 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 Abca1(ko) mice infused with scrambled Aβ, suggesting that Abca1(ko) 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 Abca1(ko) 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. |
format | Online Article Text |
id | pubmed-5302049 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | IOS Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-53020492017-02-28 ABCA1 Deficiency Affects Basal Cognitive Deficits and Dendritic Density in Mice Fitz, Nicholas F. Carter, Alexis Y. Tapias, Victor Castranio, Emilie L. Kodali, Ravindra Lefterov, Iliya Koldamova, Radosveta J Alzheimers Dis Research Article 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 Abca1(ko) and wild-type (WT) mice. We also examined the effect of intra-hippocampal infused Aβ oligomers on cognitive performance of Abca1(ko) 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 Abca1(ko) mice infused with scrambled Aβ, suggesting that Abca1(ko) 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 Abca1(ko) 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. IOS Press 2017-02-03 /pmc/articles/PMC5302049/ /pubmed/28106559 http://dx.doi.org/10.3233/JAD-161056 Text en IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Fitz, Nicholas F. Carter, Alexis Y. Tapias, Victor Castranio, Emilie L. Kodali, Ravindra Lefterov, Iliya Koldamova, Radosveta ABCA1 Deficiency Affects Basal Cognitive Deficits and Dendritic Density in Mice |
title | ABCA1 Deficiency Affects Basal Cognitive Deficits and Dendritic Density in Mice |
title_full | ABCA1 Deficiency Affects Basal Cognitive Deficits and Dendritic Density in Mice |
title_fullStr | ABCA1 Deficiency Affects Basal Cognitive Deficits and Dendritic Density in Mice |
title_full_unstemmed | ABCA1 Deficiency Affects Basal Cognitive Deficits and Dendritic Density in Mice |
title_short | ABCA1 Deficiency Affects Basal Cognitive Deficits and Dendritic Density in Mice |
title_sort | abca1 deficiency affects basal cognitive deficits and dendritic density in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5302049/ https://www.ncbi.nlm.nih.gov/pubmed/28106559 http://dx.doi.org/10.3233/JAD-161056 |
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