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Dysregulation of Amyloid-β Protein Precursor, β-Secretase, Presenilin 1 and 2 Genes in the Rat Selectively Vulnerable CA1 Subfield of Hippocampus Following Transient Global Brain Ischemia
The interaction between brain ischemia and Alzheimer’s disease (AD) has been intensively investigated recently. Nevertheless, we have not yet understood the nature and mechanisms of the ischemic episodes triggering the onset of AD and how they influence its slow progression. The assumed connection b...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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IOS Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923727/ https://www.ncbi.nlm.nih.gov/pubmed/26401782 http://dx.doi.org/10.3233/JAD-150299 |
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author | Kocki, Janusz Ułamek-Kozioł, Marzena Bogucka-Kocka, Anna Januszewski, Sławomir Jabłoński, Mirosław Gil-Kulik, Paulina Brzozowska, Judyta Petniak, Alicja Furmaga-Jabłońska, Wanda Bogucki, Jacek Czuczwar, Stanisław J. Pluta, Ryszard |
author_facet | Kocki, Janusz Ułamek-Kozioł, Marzena Bogucka-Kocka, Anna Januszewski, Sławomir Jabłoński, Mirosław Gil-Kulik, Paulina Brzozowska, Judyta Petniak, Alicja Furmaga-Jabłońska, Wanda Bogucki, Jacek Czuczwar, Stanisław J. Pluta, Ryszard |
author_sort | Kocki, Janusz |
collection | PubMed |
description | The interaction between brain ischemia and Alzheimer’s disease (AD) has been intensively investigated recently. Nevertheless, we have not yet understood the nature and mechanisms of the ischemic episodes triggering the onset of AD and how they influence its slow progression. The assumed connection between brain ischemia and the accumulation of amyloid-β (Aβ) peptide awaits to be clearly explained. In our research, we employed a rat cardiac arrest model to study the changes in gene expression of amyloid-β protein precursor (AβPP) and its cleaving enzymes, β- and γ-secretases (including presenilins) in hippocampal CA1 sector, following transient 10-min global brain ischemia. The quantitative reverse-transcriptase PCR assay demonstrated that the expression of all above genes that contribute to Aβ peptide generation was dysregulated during 30 days in postischemic hippocampal CA1 area. It suggests that studied Aβ peptide generation-related genes can be involved in AβPP metabolism, following global brain ischemia and will be useful to identify the molecular mechanisms underpinning that cerebral ischemia might be an etiological cause of AD via dysregulation of AβPP and its cleaving enzymes, β- and γ-secretases genes, and subsequently, it may increase Aβ peptide production and promote the gradual and slow development of AD neuropathology. Our data demonstrate that brain ischemia activates delayed neuronal death in hippocampus in an AβPP-dependent manner, thus defining a new and important mode of ischemic cell death. |
format | Online Article Text |
id | pubmed-4923727 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | IOS Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-49237272016-06-29 Dysregulation of Amyloid-β Protein Precursor, β-Secretase, Presenilin 1 and 2 Genes in the Rat Selectively Vulnerable CA1 Subfield of Hippocampus Following Transient Global Brain Ischemia Kocki, Janusz Ułamek-Kozioł, Marzena Bogucka-Kocka, Anna Januszewski, Sławomir Jabłoński, Mirosław Gil-Kulik, Paulina Brzozowska, Judyta Petniak, Alicja Furmaga-Jabłońska, Wanda Bogucki, Jacek Czuczwar, Stanisław J. Pluta, Ryszard J Alzheimers Dis Research Article The interaction between brain ischemia and Alzheimer’s disease (AD) has been intensively investigated recently. Nevertheless, we have not yet understood the nature and mechanisms of the ischemic episodes triggering the onset of AD and how they influence its slow progression. The assumed connection between brain ischemia and the accumulation of amyloid-β (Aβ) peptide awaits to be clearly explained. In our research, we employed a rat cardiac arrest model to study the changes in gene expression of amyloid-β protein precursor (AβPP) and its cleaving enzymes, β- and γ-secretases (including presenilins) in hippocampal CA1 sector, following transient 10-min global brain ischemia. The quantitative reverse-transcriptase PCR assay demonstrated that the expression of all above genes that contribute to Aβ peptide generation was dysregulated during 30 days in postischemic hippocampal CA1 area. It suggests that studied Aβ peptide generation-related genes can be involved in AβPP metabolism, following global brain ischemia and will be useful to identify the molecular mechanisms underpinning that cerebral ischemia might be an etiological cause of AD via dysregulation of AβPP and its cleaving enzymes, β- and γ-secretases genes, and subsequently, it may increase Aβ peptide production and promote the gradual and slow development of AD neuropathology. Our data demonstrate that brain ischemia activates delayed neuronal death in hippocampus in an AβPP-dependent manner, thus defining a new and important mode of ischemic cell death. IOS Press 2015-08-11 /pmc/articles/PMC4923727/ /pubmed/26401782 http://dx.doi.org/10.3233/JAD-150299 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 Kocki, Janusz Ułamek-Kozioł, Marzena Bogucka-Kocka, Anna Januszewski, Sławomir Jabłoński, Mirosław Gil-Kulik, Paulina Brzozowska, Judyta Petniak, Alicja Furmaga-Jabłońska, Wanda Bogucki, Jacek Czuczwar, Stanisław J. Pluta, Ryszard Dysregulation of Amyloid-β Protein Precursor, β-Secretase, Presenilin 1 and 2 Genes in the Rat Selectively Vulnerable CA1 Subfield of Hippocampus Following Transient Global Brain Ischemia |
title | Dysregulation of Amyloid-β Protein Precursor, β-Secretase, Presenilin 1 and 2 Genes in the Rat Selectively Vulnerable CA1 Subfield of Hippocampus Following Transient Global Brain Ischemia |
title_full | Dysregulation of Amyloid-β Protein Precursor, β-Secretase, Presenilin 1 and 2 Genes in the Rat Selectively Vulnerable CA1 Subfield of Hippocampus Following Transient Global Brain Ischemia |
title_fullStr | Dysregulation of Amyloid-β Protein Precursor, β-Secretase, Presenilin 1 and 2 Genes in the Rat Selectively Vulnerable CA1 Subfield of Hippocampus Following Transient Global Brain Ischemia |
title_full_unstemmed | Dysregulation of Amyloid-β Protein Precursor, β-Secretase, Presenilin 1 and 2 Genes in the Rat Selectively Vulnerable CA1 Subfield of Hippocampus Following Transient Global Brain Ischemia |
title_short | Dysregulation of Amyloid-β Protein Precursor, β-Secretase, Presenilin 1 and 2 Genes in the Rat Selectively Vulnerable CA1 Subfield of Hippocampus Following Transient Global Brain Ischemia |
title_sort | dysregulation of amyloid-β protein precursor, β-secretase, presenilin 1 and 2 genes in the rat selectively vulnerable ca1 subfield of hippocampus following transient global brain ischemia |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923727/ https://www.ncbi.nlm.nih.gov/pubmed/26401782 http://dx.doi.org/10.3233/JAD-150299 |
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