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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2023
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.
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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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