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Early Hippocampal i-LTP and LOX-1 Overexpression Induced by Anoxia: A Potential Role in Neurodegeneration in NPC Mouse Model
Niemann-Pick type C disease (NPCD) is an autosomal recessive storage disorder, characterized by abnormal sequestration of unesterified cholesterol within the late endo-lysosomal compartment of cells. In the central nervous system, hypoxic insults could result in low-density lipoprotein (LDL) oxidati...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535933/ https://www.ncbi.nlm.nih.gov/pubmed/28678158 http://dx.doi.org/10.3390/ijms18071442 |
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author | Lo Castro, Adriana Murdocca, Michela Pucci, Sabina Zaratti, Anna Greggi, Chiara Sangiuolo, Federica Tancredi, Virginia Frank, Claudio D’Arcangelo, Giovanna |
author_facet | Lo Castro, Adriana Murdocca, Michela Pucci, Sabina Zaratti, Anna Greggi, Chiara Sangiuolo, Federica Tancredi, Virginia Frank, Claudio D’Arcangelo, Giovanna |
author_sort | Lo Castro, Adriana |
collection | PubMed |
description | Niemann-Pick type C disease (NPCD) is an autosomal recessive storage disorder, characterized by abnormal sequestration of unesterified cholesterol within the late endo-lysosomal compartment of cells. In the central nervous system, hypoxic insults could result in low-density lipoprotein (LDL) oxidation and Lectin-like oxidized LDL receptor-1 (LOX-1) induction, leading to a pathological hippocampal response, namely, ischemic long-term potentiation (i-LTP). These events may correlate with the progressive neural loss observed in NPCD. To test these hypotheses, hippocampal slices from Wild Type (WT) and NPC1(−/−) mice were prepared, and field potential in the CA1 region was analyzed during transient oxygen/glucose deprivation (OGD). Moreover, LOX-1 expression was evaluated by RT-qPCR, immunocytochemical, and Western blot analyses before and after an anoxic episode. Our results demonstrate the development of a precocious i-LTP in NPC1(−/−) mice during OGD application. We also observed a higher expression of LOX-1 transcript and protein in NPC1(−/−) mice with respect to WT mice; after anoxic damage to LOX-1 expression, a further increase in both NPC1(−/−) and WT mice was observed, although the protein expression seems to be delayed, suggesting a different kinetic of induction. These data clearly suggest an elevated susceptibility to neurodegeneration in NPC1(−/−) mice due to oxidative stress. The observed up-regulation of LOX-1 in the hippocampus of NPC1(−/−) mice may also open a new scenario in which new biomarkers can be identified. |
format | Online Article Text |
id | pubmed-5535933 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-55359332017-08-04 Early Hippocampal i-LTP and LOX-1 Overexpression Induced by Anoxia: A Potential Role in Neurodegeneration in NPC Mouse Model Lo Castro, Adriana Murdocca, Michela Pucci, Sabina Zaratti, Anna Greggi, Chiara Sangiuolo, Federica Tancredi, Virginia Frank, Claudio D’Arcangelo, Giovanna Int J Mol Sci Communication Niemann-Pick type C disease (NPCD) is an autosomal recessive storage disorder, characterized by abnormal sequestration of unesterified cholesterol within the late endo-lysosomal compartment of cells. In the central nervous system, hypoxic insults could result in low-density lipoprotein (LDL) oxidation and Lectin-like oxidized LDL receptor-1 (LOX-1) induction, leading to a pathological hippocampal response, namely, ischemic long-term potentiation (i-LTP). These events may correlate with the progressive neural loss observed in NPCD. To test these hypotheses, hippocampal slices from Wild Type (WT) and NPC1(−/−) mice were prepared, and field potential in the CA1 region was analyzed during transient oxygen/glucose deprivation (OGD). Moreover, LOX-1 expression was evaluated by RT-qPCR, immunocytochemical, and Western blot analyses before and after an anoxic episode. Our results demonstrate the development of a precocious i-LTP in NPC1(−/−) mice during OGD application. We also observed a higher expression of LOX-1 transcript and protein in NPC1(−/−) mice with respect to WT mice; after anoxic damage to LOX-1 expression, a further increase in both NPC1(−/−) and WT mice was observed, although the protein expression seems to be delayed, suggesting a different kinetic of induction. These data clearly suggest an elevated susceptibility to neurodegeneration in NPC1(−/−) mice due to oxidative stress. The observed up-regulation of LOX-1 in the hippocampus of NPC1(−/−) mice may also open a new scenario in which new biomarkers can be identified. MDPI 2017-07-05 /pmc/articles/PMC5535933/ /pubmed/28678158 http://dx.doi.org/10.3390/ijms18071442 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Lo Castro, Adriana Murdocca, Michela Pucci, Sabina Zaratti, Anna Greggi, Chiara Sangiuolo, Federica Tancredi, Virginia Frank, Claudio D’Arcangelo, Giovanna Early Hippocampal i-LTP and LOX-1 Overexpression Induced by Anoxia: A Potential Role in Neurodegeneration in NPC Mouse Model |
title | Early Hippocampal i-LTP and LOX-1 Overexpression Induced by Anoxia: A Potential Role in Neurodegeneration in NPC Mouse Model |
title_full | Early Hippocampal i-LTP and LOX-1 Overexpression Induced by Anoxia: A Potential Role in Neurodegeneration in NPC Mouse Model |
title_fullStr | Early Hippocampal i-LTP and LOX-1 Overexpression Induced by Anoxia: A Potential Role in Neurodegeneration in NPC Mouse Model |
title_full_unstemmed | Early Hippocampal i-LTP and LOX-1 Overexpression Induced by Anoxia: A Potential Role in Neurodegeneration in NPC Mouse Model |
title_short | Early Hippocampal i-LTP and LOX-1 Overexpression Induced by Anoxia: A Potential Role in Neurodegeneration in NPC Mouse Model |
title_sort | early hippocampal i-ltp and lox-1 overexpression induced by anoxia: a potential role in neurodegeneration in npc mouse model |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535933/ https://www.ncbi.nlm.nih.gov/pubmed/28678158 http://dx.doi.org/10.3390/ijms18071442 |
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