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Synuclein deficiency results in age-related respiratory and cardiovascular dysfunctions in mice

Hosford, Patrick S., Ninkina, Natalia ORCID:, Buchman, Vladimir L. ORCID:, Smith, Jeffrey C., Marina, Nephtali and SheikhBahaei, Shahriar 2020. Synuclein deficiency results in age-related respiratory and cardiovascular dysfunctions in mice. Brain Sciences 10 (9) , 583. 10.3390/brainsci10090583

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: MDPI
ISSN: 2076-3425
Date of First Compliant Deposit: 30 September 2020
Date of Acceptance: 20 August 2020
Last Modified: 27 Nov 2022 12:16

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