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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2015
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.
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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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