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Comparative benefits of simvastatin and exercise in a mouse model of vascular cognitive impairment and dementia
Aerobic physical exercise (EX) and controlling cardiovascular risk factors in midlife can improve and protect cognitive function in healthy individuals and are considered to be effective at reducing late-onset dementia incidence. By investigating commonalities between these preventative approaches,...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Federation of American Societies for Experimental Biology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894065/ https://www.ncbi.nlm.nih.gov/pubmed/31557051 http://dx.doi.org/10.1096/fj.201901002R |
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author | Trigiani, Lianne J. Royea, Jessika Tong, Xin-Kang Hamel, Edith |
author_facet | Trigiani, Lianne J. Royea, Jessika Tong, Xin-Kang Hamel, Edith |
author_sort | Trigiani, Lianne J. |
collection | PubMed |
description | Aerobic physical exercise (EX) and controlling cardiovascular risk factors in midlife can improve and protect cognitive function in healthy individuals and are considered to be effective at reducing late-onset dementia incidence. By investigating commonalities between these preventative approaches, we sought to identify possible targets for effective interventions. We compared the efficacy of EX and simvastatin (SV) pharmacotherapy to counteract cognitive deficits induced by a high-cholesterol diet (2%, HCD) in mice overexpressing TGF-β1 (TGF mice), a model of vascular cognitive impairment and dementia. Cognitive deficits were found in hypercholesterolemic mice for object recognition memory, and both SV and EX prevented this decline. EX improved stimulus-evoked cerebral blood flow responses and was as effective as SV in normalizing endothelium-dependent vasodilatory responses in cerebral arteries. The up-regulation of galectin-3–positive microglial cells in white matter (WM) of HCD-fed TGF mice with cognitive deficits was significantly reduced by both SV and EX concurrently with cognitive recovery. Altered hippocampal neurogenesis, gray matter astrogliosis, or microgliosis did not correlate with cognitive deficits or benefits. Overall, results indicate that SV and EX prevented cognitive decline in hypercholesterolemic mice and that they share common sites of action in preventing endothelial cell dysfunction and reducing WM inflammation.—Trigiani, L. J., Royea, J., Tong, X.-K., Hamel, E. Comparative benefits of simvastatin and exercise in a mouse model of vascular cognitive impairment and dementia. |
format | Online Article Text |
id | pubmed-6894065 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Federation of American Societies for Experimental Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-68940652019-12-10 Comparative benefits of simvastatin and exercise in a mouse model of vascular cognitive impairment and dementia Trigiani, Lianne J. Royea, Jessika Tong, Xin-Kang Hamel, Edith FASEB J Research Aerobic physical exercise (EX) and controlling cardiovascular risk factors in midlife can improve and protect cognitive function in healthy individuals and are considered to be effective at reducing late-onset dementia incidence. By investigating commonalities between these preventative approaches, we sought to identify possible targets for effective interventions. We compared the efficacy of EX and simvastatin (SV) pharmacotherapy to counteract cognitive deficits induced by a high-cholesterol diet (2%, HCD) in mice overexpressing TGF-β1 (TGF mice), a model of vascular cognitive impairment and dementia. Cognitive deficits were found in hypercholesterolemic mice for object recognition memory, and both SV and EX prevented this decline. EX improved stimulus-evoked cerebral blood flow responses and was as effective as SV in normalizing endothelium-dependent vasodilatory responses in cerebral arteries. The up-regulation of galectin-3–positive microglial cells in white matter (WM) of HCD-fed TGF mice with cognitive deficits was significantly reduced by both SV and EX concurrently with cognitive recovery. Altered hippocampal neurogenesis, gray matter astrogliosis, or microgliosis did not correlate with cognitive deficits or benefits. Overall, results indicate that SV and EX prevented cognitive decline in hypercholesterolemic mice and that they share common sites of action in preventing endothelial cell dysfunction and reducing WM inflammation.—Trigiani, L. J., Royea, J., Tong, X.-K., Hamel, E. Comparative benefits of simvastatin and exercise in a mouse model of vascular cognitive impairment and dementia. Federation of American Societies for Experimental Biology 2019-12 2019-09-26 /pmc/articles/PMC6894065/ /pubmed/31557051 http://dx.doi.org/10.1096/fj.201901002R Text en © The Author(s) https://creativecommons.org/licenses/by-nc-nd/2.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 2.0 International (CC BY-NC-ND 2.0) (https://creativecommons.org/licenses/by-nc-nd/2.0/) which permits noncommercial use, distribution, and reproduction in any medium, but prohibits the publication/distribution of derivative works, provided the original work is properly cited. |
spellingShingle | Research Trigiani, Lianne J. Royea, Jessika Tong, Xin-Kang Hamel, Edith Comparative benefits of simvastatin and exercise in a mouse model of vascular cognitive impairment and dementia |
title | Comparative benefits of simvastatin and exercise in a mouse model of vascular cognitive impairment and dementia |
title_full | Comparative benefits of simvastatin and exercise in a mouse model of vascular cognitive impairment and dementia |
title_fullStr | Comparative benefits of simvastatin and exercise in a mouse model of vascular cognitive impairment and dementia |
title_full_unstemmed | Comparative benefits of simvastatin and exercise in a mouse model of vascular cognitive impairment and dementia |
title_short | Comparative benefits of simvastatin and exercise in a mouse model of vascular cognitive impairment and dementia |
title_sort | comparative benefits of simvastatin and exercise in a mouse model of vascular cognitive impairment and dementia |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6894065/ https://www.ncbi.nlm.nih.gov/pubmed/31557051 http://dx.doi.org/10.1096/fj.201901002R |
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