Age-Dependent Alterations of Cognition, Mitochondrial Function, and Beta-Amyloid Deposition in a Murine Model of Alzheimer’s Disease—A Longitudinal Study
Aging is the main risk factor for sporadic Alzheimer’s disease (AD), which is characterized by the cerebral deposition of β-amyloid peptides (Aβ) and cognitive decline. Mitochondrial dysfunction is also characteristic of the disease and represents a hallmark of both, aging and neurodegeneration. We...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2022.875989/full |
| _version_ | 1817983388087222272 |
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| author | Martina Reutzel Rekha Grewal Aljoscha Joppe Gunter P. Eckert |
| author_facet | Martina Reutzel Rekha Grewal Aljoscha Joppe Gunter P. Eckert |
| author_sort | Martina Reutzel |
| collection | DOAJ |
| description | Aging is the main risk factor for sporadic Alzheimer’s disease (AD), which is characterized by the cerebral deposition of β-amyloid peptides (Aβ) and cognitive decline. Mitochondrial dysfunction is also characteristic of the disease and represents a hallmark of both, aging and neurodegeneration. We longitudinally followed Aβ levels, cognition, and mitochondrial function in the same cohort of Thy1-APP751SL mice representing a murine model of AD. In the course of time, changes were most prominent at an age of 13 months including the latency time in the passive avoidance test, the activity of complexes I and IV of the mitochondrial respiration chain, and expression of genes related to mitochondrial biogenesis and synaptic plasticity including Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), CAMP responsive element binding protein 1 (CREB1), and Synaptophysin 1 (SYP1). These changes occurred in parallel with massively increasing cerebral Aβ levels. Other parameters were changed in younger mice including the alteration rate in the Y-maze test and the nesting score when Aβ levels were not changed yet. The results are consistent in the cohort described. However, previous, non-longitudinal studies reported divergent time points for the occurrence of the parameters studied. These findings are discussed in light of the current results. |
| first_indexed | 2024-04-13T23:31:46Z |
| format | Article |
| id | doaj.art-83830320b96c496099e1057b85a44880 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-04-13T23:31:46Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-83830320b96c496099e1057b85a448802022-12-22T02:24:52ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652022-05-011410.3389/fnagi.2022.875989875989Age-Dependent Alterations of Cognition, Mitochondrial Function, and Beta-Amyloid Deposition in a Murine Model of Alzheimer’s Disease—A Longitudinal StudyMartina Reutzel0Rekha Grewal1Aljoscha Joppe2Gunter P. Eckert3Laboratory for Nutrition in Prevention and Therapy, Biomedical Research Center Seltersberg (BFS), Institute of Nutritional Sciences, Justus-Liebig-University Giessen, Giessen, GermanyLaboratory for Nutrition in Prevention and Therapy, Biomedical Research Center Seltersberg (BFS), Institute of Nutritional Sciences, Justus-Liebig-University Giessen, Giessen, GermanyDepartment of Biological Sciences & Cluster of Excellence Macromolecular Complexes, Institute for Molecular Biosciences, Johann Wolfgang Goethe-University Frankfurt, Frankfurt am Main, GermanyLaboratory for Nutrition in Prevention and Therapy, Biomedical Research Center Seltersberg (BFS), Institute of Nutritional Sciences, Justus-Liebig-University Giessen, Giessen, GermanyAging is the main risk factor for sporadic Alzheimer’s disease (AD), which is characterized by the cerebral deposition of β-amyloid peptides (Aβ) and cognitive decline. Mitochondrial dysfunction is also characteristic of the disease and represents a hallmark of both, aging and neurodegeneration. We longitudinally followed Aβ levels, cognition, and mitochondrial function in the same cohort of Thy1-APP751SL mice representing a murine model of AD. In the course of time, changes were most prominent at an age of 13 months including the latency time in the passive avoidance test, the activity of complexes I and IV of the mitochondrial respiration chain, and expression of genes related to mitochondrial biogenesis and synaptic plasticity including Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), CAMP responsive element binding protein 1 (CREB1), and Synaptophysin 1 (SYP1). These changes occurred in parallel with massively increasing cerebral Aβ levels. Other parameters were changed in younger mice including the alteration rate in the Y-maze test and the nesting score when Aβ levels were not changed yet. The results are consistent in the cohort described. However, previous, non-longitudinal studies reported divergent time points for the occurrence of the parameters studied. These findings are discussed in light of the current results.https://www.frontiersin.org/articles/10.3389/fnagi.2022.875989/fullmitochondrial dysfunctionamyloid-betaAlzheimers’s diseasetransgenic mouse modelslongitudinal studies |
| spellingShingle | Martina Reutzel Rekha Grewal Aljoscha Joppe Gunter P. Eckert Age-Dependent Alterations of Cognition, Mitochondrial Function, and Beta-Amyloid Deposition in a Murine Model of Alzheimer’s Disease—A Longitudinal Study Frontiers in Aging Neuroscience mitochondrial dysfunction amyloid-beta Alzheimers’s disease transgenic mouse models longitudinal studies |
| title | Age-Dependent Alterations of Cognition, Mitochondrial Function, and Beta-Amyloid Deposition in a Murine Model of Alzheimer’s Disease—A Longitudinal Study |
| title_full | Age-Dependent Alterations of Cognition, Mitochondrial Function, and Beta-Amyloid Deposition in a Murine Model of Alzheimer’s Disease—A Longitudinal Study |
| title_fullStr | Age-Dependent Alterations of Cognition, Mitochondrial Function, and Beta-Amyloid Deposition in a Murine Model of Alzheimer’s Disease—A Longitudinal Study |
| title_full_unstemmed | Age-Dependent Alterations of Cognition, Mitochondrial Function, and Beta-Amyloid Deposition in a Murine Model of Alzheimer’s Disease—A Longitudinal Study |
| title_short | Age-Dependent Alterations of Cognition, Mitochondrial Function, and Beta-Amyloid Deposition in a Murine Model of Alzheimer’s Disease—A Longitudinal Study |
| title_sort | age dependent alterations of cognition mitochondrial function and beta amyloid deposition in a murine model of alzheimer s disease a longitudinal study |
| topic | mitochondrial dysfunction amyloid-beta Alzheimers’s disease transgenic mouse models longitudinal studies |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2022.875989/full |
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