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.
abstract: 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.
authors.affiliation: Department of Clinical Genetics, Medical University of Lublin, Lublin, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Kocki
authors.affiliation: Laboratory of Ischemic and Neurodegenerative Brain Research, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Marzena
authors.initials: M
authors.lastname: Ułamek-Kozioł
authors.affiliation: Department of Pharmaceutical Botany, Medical University of Lublin, Lublin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Bogucka-Kocka
authors.affiliation: Laboratory of Ischemic and Neurodegenerative Brain Research, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Sławomir
authors.initials: S
authors.lastname: Januszewski
authors.affiliation: Department of Rehabilitation and Orthopaedics, Medical University of Lublin, Lublin, Poland.
authors.forename: Mirosław
authors.initials: M
authors.lastname: Jabłoński
authors.affiliation: Department of Clinical Genetics, Medical University of Lublin, Lublin, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Gil-Kulik
authors.affiliation: Department of Clinical Psychology, Medical University of Lublin, Lublin, Poland.
authors.forename: Judyta
authors.initials: J
authors.lastname: Brzozowska
authors.affiliation: Department of Clinical Genetics, Medical University of Lublin, Lublin, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Petniak
authors.affiliation: Department of Neonate and Infant Pathology, Medical University of Lublin, Lublin, Poland.
authors.forename: Wanda
authors.initials: W
authors.lastname: Furmaga-Jabłońska
authors.affiliation: Warsaw Higher Humanistic School, Warsaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Bogucki
authors.affiliation: Department of Pathophysiology, Medical University of Lublin, Lublin, Poland.|Department of Physiopathology, Institute of Rural Medicine, Lublin, Poland.
authors.forename: Stanisław J
authors.initials: SJ
authors.lastname: Czuczwar
authors.affiliation: Laboratory of Ischemic and Neurodegenerative Brain Research, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Pluta
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006323:Heart Arrest; D053764:Presenilin-1 / Q000378:metabolism*; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; C000607793:Psen1 protein, rat; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat
keywords: Alzheimer’s disease; CA1 area; amyloid-β protein precursor; brain ischemia; dementia; genes; hippocampus; presenilin 1 and 2; β-secretase; γ-secretase