Age-Related Inflammatory Balance Shift, Nasal Barrier Function, and Cerebro-Morphological Status in Healthy and Diseased Rodents
Increased blood–brain barrier (BBB) permeability and extensive neuronal changes have been described earlier in both healthy and pathological aging like apolipoprotein B-100 (APOB-100) and amyloid precursor protein (APP)–presenilin-1 (PSEN1) transgenic mouse models. APOB-100 hypertriglyceridemic mode...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2021.700729/full |
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| author | Zsófia Varga-Medveczky Noémi Kovács Melinda E. Tóth Miklós Sántha Ildikó Horváth Luca Anna Bors Luca Anna Bors Katalin Fónagy Timea Imre Pál Szabó Domokos Máthé Domokos Máthé Franciska Erdő |
| author_facet | Zsófia Varga-Medveczky Noémi Kovács Melinda E. Tóth Miklós Sántha Ildikó Horváth Luca Anna Bors Luca Anna Bors Katalin Fónagy Timea Imre Pál Szabó Domokos Máthé Domokos Máthé Franciska Erdő |
| author_sort | Zsófia Varga-Medveczky |
| collection | DOAJ |
| description | Increased blood–brain barrier (BBB) permeability and extensive neuronal changes have been described earlier in both healthy and pathological aging like apolipoprotein B-100 (APOB-100) and amyloid precursor protein (APP)–presenilin-1 (PSEN1) transgenic mouse models. APOB-100 hypertriglyceridemic model is a useful tool to study the link between cerebrovascular pathology and neurodegeneration, while APP–PSEN1 humanized mouse is a model of Alzheimer’s disease. The aim of the current study was to characterize the inflammatory changes in the brain with healthy aging and in neurodegeneration. Also, the cerebro-morphological and cognitive alterations have been investigated. The nose-to-brain delivery of a P-glycoprotein substrate model drug (quinidine) was monitored in the disease models and compared with the age-matched controls. Our results revealed an inflammatory balance shift in both the healthy aged and neurodegenerative models. In normal aging monocyte chemoattractant protein-1, stem cell factor and Rantes were highly upregulated indicating a stimulated leukocyte status. In APOB-100 mice, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF-BB), and interleukin-17A (IL-17A) were induced (vascular reaction), while in APP–PSEN1 mice resistin, IL-17A and GM-CSF were mostly upregulated. The nasal drug absorption was similar in the brain and blood indicating the molecular bypass of the BBB. The learning and memory tests showed no difference in the cognitive performance of healthy aged and young animals. Based on these results, it can be concluded that various markers of chronic inflammation are present in healthy aged and diseased animals. In APOB-100 mice, a cerebro-ventricular dilation can also be observed. For development of proper anti-aging and neuroprotective compounds, further studies focusing on the above inflammatory targets are suggested. |
| first_indexed | 2024-12-20T00:39:03Z |
| format | Article |
| id | doaj.art-80f18d5de08c4131af27e6b7231b4ecf |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-20T00:39:03Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-80f18d5de08c4131af27e6b7231b4ecf2022-12-21T19:59:40ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2021-07-011510.3389/fnins.2021.700729700729Age-Related Inflammatory Balance Shift, Nasal Barrier Function, and Cerebro-Morphological Status in Healthy and Diseased RodentsZsófia Varga-Medveczky0Noémi Kovács1Melinda E. Tóth2Miklós Sántha3Ildikó Horváth4Luca Anna Bors5Luca Anna Bors6Katalin Fónagy7Timea Imre8Pál Szabó9Domokos Máthé10Domokos Máthé11Franciska Erdő12Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, HungaryDepartment of Biophysics and Radiation Biology, Faculty of Medicine, Semmelweis University, Budapest, HungaryInstitute of Biochemistry, ELKH Biological Research Centre, Szeged, HungaryInstitute of Biochemistry, ELKH Biological Research Centre, Szeged, HungaryDepartment of Biophysics and Radiation Biology, Faculty of Medicine, Semmelweis University, Budapest, HungaryFaculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, HungaryHeart and Vascular Centre, Faculty of Medicine, Semmelweis University, Budapest, HungaryFaculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, HungaryResearch Centre for Natural Sciences, Centre for Structural Study, Budapest, HungaryResearch Centre for Natural Sciences, Centre for Structural Study, Budapest, HungaryDepartment of Biophysics and Radiation Biology, Faculty of Medicine, Semmelweis University, Budapest, HungaryHungarian Center of Excellence for Molecular Medicine (HCEMM), Advanced In Vivo Imaging Core Faciltiy, Budapest, HungaryFaculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, HungaryIncreased blood–brain barrier (BBB) permeability and extensive neuronal changes have been described earlier in both healthy and pathological aging like apolipoprotein B-100 (APOB-100) and amyloid precursor protein (APP)–presenilin-1 (PSEN1) transgenic mouse models. APOB-100 hypertriglyceridemic model is a useful tool to study the link between cerebrovascular pathology and neurodegeneration, while APP–PSEN1 humanized mouse is a model of Alzheimer’s disease. The aim of the current study was to characterize the inflammatory changes in the brain with healthy aging and in neurodegeneration. Also, the cerebro-morphological and cognitive alterations have been investigated. The nose-to-brain delivery of a P-glycoprotein substrate model drug (quinidine) was monitored in the disease models and compared with the age-matched controls. Our results revealed an inflammatory balance shift in both the healthy aged and neurodegenerative models. In normal aging monocyte chemoattractant protein-1, stem cell factor and Rantes were highly upregulated indicating a stimulated leukocyte status. In APOB-100 mice, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF-BB), and interleukin-17A (IL-17A) were induced (vascular reaction), while in APP–PSEN1 mice resistin, IL-17A and GM-CSF were mostly upregulated. The nasal drug absorption was similar in the brain and blood indicating the molecular bypass of the BBB. The learning and memory tests showed no difference in the cognitive performance of healthy aged and young animals. Based on these results, it can be concluded that various markers of chronic inflammation are present in healthy aged and diseased animals. In APOB-100 mice, a cerebro-ventricular dilation can also be observed. For development of proper anti-aging and neuroprotective compounds, further studies focusing on the above inflammatory targets are suggested.https://www.frontiersin.org/articles/10.3389/fnins.2021.700729/fullagingcytokinesAPOB-100 miceAPP-PSEN1 micemagnetic resonance imagingin vivo microdialysis |
| spellingShingle | Zsófia Varga-Medveczky Noémi Kovács Melinda E. Tóth Miklós Sántha Ildikó Horváth Luca Anna Bors Luca Anna Bors Katalin Fónagy Timea Imre Pál Szabó Domokos Máthé Domokos Máthé Franciska Erdő Age-Related Inflammatory Balance Shift, Nasal Barrier Function, and Cerebro-Morphological Status in Healthy and Diseased Rodents Frontiers in Neuroscience aging cytokines APOB-100 mice APP-PSEN1 mice magnetic resonance imaging in vivo microdialysis |
| title | Age-Related Inflammatory Balance Shift, Nasal Barrier Function, and Cerebro-Morphological Status in Healthy and Diseased Rodents |
| title_full | Age-Related Inflammatory Balance Shift, Nasal Barrier Function, and Cerebro-Morphological Status in Healthy and Diseased Rodents |
| title_fullStr | Age-Related Inflammatory Balance Shift, Nasal Barrier Function, and Cerebro-Morphological Status in Healthy and Diseased Rodents |
| title_full_unstemmed | Age-Related Inflammatory Balance Shift, Nasal Barrier Function, and Cerebro-Morphological Status in Healthy and Diseased Rodents |
| title_short | Age-Related Inflammatory Balance Shift, Nasal Barrier Function, and Cerebro-Morphological Status in Healthy and Diseased Rodents |
| title_sort | age related inflammatory balance shift nasal barrier function and cerebro morphological status in healthy and diseased rodents |
| topic | aging cytokines APOB-100 mice APP-PSEN1 mice magnetic resonance imaging in vivo microdialysis |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2021.700729/full |
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