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Enhanced Cerebral Hemodynamics and Cognitive Function Via Knockout of Dual-Specificity Protein Phosphatase 5
Alzheimer’s Disease (AD) and Alzheimer’s Disease-Related Dementias (ADRD) are neurodegenerative disorders. Recent studies suggest that cerebral hypoperfusion is an early symptom of AD/ADRD. Dual-specificity protein phosphatase 5 (DUSP5) has been implicated in several pathological conditions, includi...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10430881/ https://www.ncbi.nlm.nih.gov/pubmed/37588944 http://dx.doi.org/10.26502/fjppr.070 |
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author | Zhang, Huawei Border, Jane J. Fang, Xing Liu, Yedan Tang, Chengyun Gao, Wenjun Wang, Shaoxun Shin, Seung Min Guo, Ya Zhang, Chao Gonzalez-Fernandez, Ezekiel Yu, Hongwei Sun, Peng Roman, Richard J. Fan, Fan |
author_facet | Zhang, Huawei Border, Jane J. Fang, Xing Liu, Yedan Tang, Chengyun Gao, Wenjun Wang, Shaoxun Shin, Seung Min Guo, Ya Zhang, Chao Gonzalez-Fernandez, Ezekiel Yu, Hongwei Sun, Peng Roman, Richard J. Fan, Fan |
author_sort | Zhang, Huawei |
collection | PubMed |
description | Alzheimer’s Disease (AD) and Alzheimer’s Disease-Related Dementias (ADRD) are neurodegenerative disorders. Recent studies suggest that cerebral hypoperfusion is an early symptom of AD/ADRD. Dual-specificity protein phosphatase 5 (DUSP5) has been implicated in several pathological conditions, including pulmonary hypertension and cancer, but its role in AD/ADRD remains unclear. The present study builds on our previous findings, demonstrating that inhibition of ERK and PKC leads to a dose-dependent dilation of the middle cerebral artery and penetrating arteriole, with a more pronounced effect in Dusp5 KO rats. Both ERK and PKC inhibitors resulted in a significant reduction of myogenic tone in vessels from Dusp5 KO rats. Dusp5 KO rats exhibited stronger autoregulation of the surface but not deep cortical cerebral blood flow. Inhibition of ERK and PKC significantly enhanced the contractile capacity of vascular smooth muscle cells from both strains. Finally, a significant improvement in learning and memory was observed in Dusp5 KO rats 24 hours after initial training. Our results suggest that altered vascular reactivity in Dusp5 KO rats may involve distinct mechanisms for different vascular beds, and DUSP5 deletion could be a potential therapeutic target for AD/ADRD. Further investigations are necessary to determine the effects of DUSP5 inhibition on capillary stalling, blood-brain barrier permeability, and neurodegeneration in aging and disease models. |
format | Online Article Text |
id | pubmed-10430881 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
record_format | MEDLINE/PubMed |
spelling | pubmed-104308812023-08-16 Enhanced Cerebral Hemodynamics and Cognitive Function Via Knockout of Dual-Specificity Protein Phosphatase 5 Zhang, Huawei Border, Jane J. Fang, Xing Liu, Yedan Tang, Chengyun Gao, Wenjun Wang, Shaoxun Shin, Seung Min Guo, Ya Zhang, Chao Gonzalez-Fernandez, Ezekiel Yu, Hongwei Sun, Peng Roman, Richard J. Fan, Fan J Pharm Pharmacol Res Article Alzheimer’s Disease (AD) and Alzheimer’s Disease-Related Dementias (ADRD) are neurodegenerative disorders. Recent studies suggest that cerebral hypoperfusion is an early symptom of AD/ADRD. Dual-specificity protein phosphatase 5 (DUSP5) has been implicated in several pathological conditions, including pulmonary hypertension and cancer, but its role in AD/ADRD remains unclear. The present study builds on our previous findings, demonstrating that inhibition of ERK and PKC leads to a dose-dependent dilation of the middle cerebral artery and penetrating arteriole, with a more pronounced effect in Dusp5 KO rats. Both ERK and PKC inhibitors resulted in a significant reduction of myogenic tone in vessels from Dusp5 KO rats. Dusp5 KO rats exhibited stronger autoregulation of the surface but not deep cortical cerebral blood flow. Inhibition of ERK and PKC significantly enhanced the contractile capacity of vascular smooth muscle cells from both strains. Finally, a significant improvement in learning and memory was observed in Dusp5 KO rats 24 hours after initial training. Our results suggest that altered vascular reactivity in Dusp5 KO rats may involve distinct mechanisms for different vascular beds, and DUSP5 deletion could be a potential therapeutic target for AD/ADRD. Further investigations are necessary to determine the effects of DUSP5 inhibition on capillary stalling, blood-brain barrier permeability, and neurodegeneration in aging and disease models. 2023 2023-05-12 /pmc/articles/PMC10430881/ /pubmed/37588944 http://dx.doi.org/10.26502/fjppr.070 Text en https://creativecommons.org/licenses/by/4.0/This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license 4.0 (https://creativecommons.org/licenses/by/4.0/) |
spellingShingle | Article Zhang, Huawei Border, Jane J. Fang, Xing Liu, Yedan Tang, Chengyun Gao, Wenjun Wang, Shaoxun Shin, Seung Min Guo, Ya Zhang, Chao Gonzalez-Fernandez, Ezekiel Yu, Hongwei Sun, Peng Roman, Richard J. Fan, Fan Enhanced Cerebral Hemodynamics and Cognitive Function Via Knockout of Dual-Specificity Protein Phosphatase 5 |
title | Enhanced Cerebral Hemodynamics and Cognitive Function Via Knockout of Dual-Specificity Protein Phosphatase 5 |
title_full | Enhanced Cerebral Hemodynamics and Cognitive Function Via Knockout of Dual-Specificity Protein Phosphatase 5 |
title_fullStr | Enhanced Cerebral Hemodynamics and Cognitive Function Via Knockout of Dual-Specificity Protein Phosphatase 5 |
title_full_unstemmed | Enhanced Cerebral Hemodynamics and Cognitive Function Via Knockout of Dual-Specificity Protein Phosphatase 5 |
title_short | Enhanced Cerebral Hemodynamics and Cognitive Function Via Knockout of Dual-Specificity Protein Phosphatase 5 |
title_sort | enhanced cerebral hemodynamics and cognitive function via knockout of dual-specificity protein phosphatase 5 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10430881/ https://www.ncbi.nlm.nih.gov/pubmed/37588944 http://dx.doi.org/10.26502/fjppr.070 |
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