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Synuclein Deficiency Results in Age-Related Respiratory and Cardiovascular Dysfunctions in Mice

Synuclein (α, β, and γ) proteins are highly expressed in presynaptic terminals, and significant data exist supporting their role in regulating neurotransmitter release. Targeting the gene encoding α-synuclein is the basis of many animal models of Parkinson’s disease (PD). However, the physiological...

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Autores principales: Hosford, Patrick S., Ninkina, Natalia, Buchman, Vladimir L., Smith, Jeffrey C., Marina, Nephtali, SheikhBahaei, Shahriar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563345/
https://www.ncbi.nlm.nih.gov/pubmed/32846874
http://dx.doi.org/10.3390/brainsci10090583
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author Hosford, Patrick S.
Ninkina, Natalia
Buchman, Vladimir L.
Smith, Jeffrey C.
Marina, Nephtali
SheikhBahaei, Shahriar
author_facet Hosford, Patrick S.
Ninkina, Natalia
Buchman, Vladimir L.
Smith, Jeffrey C.
Marina, Nephtali
SheikhBahaei, Shahriar
author_sort Hosford, Patrick S.
collection PubMed
description Synuclein (α, β, and γ) proteins are highly expressed in presynaptic terminals, and significant data exist supporting their role in regulating neurotransmitter release. Targeting the gene encoding α-synuclein is the basis of many animal models of Parkinson’s disease (PD). However, the physiological role of this family of proteins in not well understood and could be especially relevant as interfering with accumulation of α-synuclein level has therapeutic potential in limiting PD progression. The long-term effects of their removal are unknown and given the complex pathophysiology of PD, could exacerbate other clinical features of the disease, for example dysautonomia. In the present study, we sought to characterize the autonomic phenotypes of mice lacking all synucleins (α, β, and γ; αβγ(−/−)) in order to better understand the role of synuclein-family proteins in autonomic function. We probed respiratory and cardiovascular reflexes in conscious and anesthetized, young (4 months) and aged (18–20 months) αβγ(−/−) male mice. Aged mice displayed impaired respiratory responses to both hypoxia and hypercapnia when breathing activities were recorded in conscious animals using whole-body plethysmography. These animals were also found to be hypertensive from conscious blood pressure recordings, to have reduced pressor baroreflex gain under anesthesia, and showed reduced termination of both pressor and depressor reflexes. The present data demonstrate the importance of synuclein in the normal function of respiratory and cardiovascular reflexes during aging.
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spelling pubmed-75633452020-10-27 Synuclein Deficiency Results in Age-Related Respiratory and Cardiovascular Dysfunctions in Mice Hosford, Patrick S. Ninkina, Natalia Buchman, Vladimir L. Smith, Jeffrey C. Marina, Nephtali SheikhBahaei, Shahriar Brain Sci Article Synuclein (α, β, and γ) proteins are highly expressed in presynaptic terminals, and significant data exist supporting their role in regulating neurotransmitter release. Targeting the gene encoding α-synuclein is the basis of many animal models of Parkinson’s disease (PD). However, the physiological role of this family of proteins in not well understood and could be especially relevant as interfering with accumulation of α-synuclein level has therapeutic potential in limiting PD progression. The long-term effects of their removal are unknown and given the complex pathophysiology of PD, could exacerbate other clinical features of the disease, for example dysautonomia. In the present study, we sought to characterize the autonomic phenotypes of mice lacking all synucleins (α, β, and γ; αβγ(−/−)) in order to better understand the role of synuclein-family proteins in autonomic function. We probed respiratory and cardiovascular reflexes in conscious and anesthetized, young (4 months) and aged (18–20 months) αβγ(−/−) male mice. Aged mice displayed impaired respiratory responses to both hypoxia and hypercapnia when breathing activities were recorded in conscious animals using whole-body plethysmography. These animals were also found to be hypertensive from conscious blood pressure recordings, to have reduced pressor baroreflex gain under anesthesia, and showed reduced termination of both pressor and depressor reflexes. The present data demonstrate the importance of synuclein in the normal function of respiratory and cardiovascular reflexes during aging. MDPI 2020-08-24 /pmc/articles/PMC7563345/ /pubmed/32846874 http://dx.doi.org/10.3390/brainsci10090583 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hosford, Patrick S.
Ninkina, Natalia
Buchman, Vladimir L.
Smith, Jeffrey C.
Marina, Nephtali
SheikhBahaei, Shahriar
Synuclein Deficiency Results in Age-Related Respiratory and Cardiovascular Dysfunctions in Mice
title Synuclein Deficiency Results in Age-Related Respiratory and Cardiovascular Dysfunctions in Mice
title_full Synuclein Deficiency Results in Age-Related Respiratory and Cardiovascular Dysfunctions in Mice
title_fullStr Synuclein Deficiency Results in Age-Related Respiratory and Cardiovascular Dysfunctions in Mice
title_full_unstemmed Synuclein Deficiency Results in Age-Related Respiratory and Cardiovascular Dysfunctions in Mice
title_short Synuclein Deficiency Results in Age-Related Respiratory and Cardiovascular Dysfunctions in Mice
title_sort synuclein deficiency results in age-related respiratory and cardiovascular dysfunctions in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563345/
https://www.ncbi.nlm.nih.gov/pubmed/32846874
http://dx.doi.org/10.3390/brainsci10090583
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