Abstract
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.
Highlights
Synucleins (α, β, and γ) are a family of highly-conserved vertebrate-specific proteins, enriched in pre-synaptic terminals of neurons and thought to be involved in regulating vesicular release and recycling of neurotransmitters [1,2,3]
We found no significant difference in hemodynamic measurements between single synuclein-null (α−/−, β−/−, γ−/− ) and the double synuclein-null animals when compared to the aged control group (Table 3)
Data from our study demonstrate that aged mice lacking lacking αβγ-synuclein proteins have impaired respiratory responses to hypoxia and hypercapnia, αβγ-synuclein proteins have impaired respiratory responses to hypoxia and hypercapnia, elevated elevated blood pressure, pressor reflex failure, and reduced ability to terminate both pressor and blood pressure, pressor reflex failure, and reduced ability−/−
Summary
Synucleins (α, β, and γ) are a family of highly-conserved vertebrate-specific proteins, enriched in pre-synaptic terminals of neurons and thought to be involved in regulating vesicular release and recycling of neurotransmitters [1,2,3]. Found α-syn to be the most relevant gene in cases of idiopathic PD. There is an important role of α-syn in regulation of key stages of dopamine release, reuptake and recycling [6]. Despite playing such an important role in pathology, surprisingly little was known about the physiological role of this protein. This was, in part, due to the sequence homology of the genes encoding the three members of this protein family [7,8]. The pattern of expression, predominantly in neuronal tissues, of these three proteins has significant overlap, and while some tissues may express more than one member, generally all three are expressed simultaneously [9]
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