Regulation of blood vessels by ATP in the ventral medullary surface in a rat model of Parkinson’s disease

Parkinson’s disease (PD) patients often experience impairment of autonomic and respiratory functions. These include conditions such as orthostatic hypotension and sleep apnea, which are highly correlated with dysfunctional central chemoreception. Blood flow is a fundamental determinant of tissue CO2...

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Bibliographic Details
Published in:	Brain research bulletin Vol. 187; pp. 138 - 154
Main Authors:	Oliveira, Luiz M., Fernandes-Junior, Silvio A., Cabral, Laís M.C., Miranda, Nicole C.S., Czeisler, Catherine M., Otero, José J., Moreira, Thiago S., Takakura, Ana C.
Format:	Journal Article
Language:	English
Published:	Elsevier Inc 01-09-2022 Elsevier
Subjects:	Brainstem Chemoreception Parkinson’s disease Pial vessels Chemoreception Pial vessels Parkinson’s disease Brainstem
Online Access:	Get full text
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Summary:	Parkinson’s disease (PD) patients often experience impairment of autonomic and respiratory functions. These include conditions such as orthostatic hypotension and sleep apnea, which are highly correlated with dysfunctional central chemoreception. Blood flow is a fundamental determinant of tissue CO2/H+, yet the extent to which blood flow regulation within chemoreceptor regions contributes to respiratory behavior during neurological disease remains unknown. Here, we tested the hypothesis that 6-hydroxydopamine injection to inducing a known model of PD results in dysfunctional vascular homeostasis, biochemical dysregulation, and glial morphology of the ventral medullary surface (VMS). We show that hypercapnia (FiCO2 = 10%) induced elevated VMS pial vessel constriction in PD animals through a P2-receptor dependent mechanism. Similarly, we found a greater CO2-induced vascular constriction after ARL67156 (an ectonucleotidase inhibitor) in control and PD-induced animals. In addition, we also report that weighted gene correlational network analysis of the proteomic data showed a protein expression module differentially represented between both groups. This module showed that gene ontology enrichment for components of the ATP machinery were reduced in our PD-model compared to control animals. Altogether, our data indicate that dysfunction in purinergic signaling, potentially through altered ATP bioavailability in the VMS region, may compromise the RTN neuroglial vascular unit in a PD animal model. •CO2-induced RTN vessel constriction in PD animals through a P2-receptor dependent mechanism.•PD animal model have an abnormal function in the ATP machinery.•Neurovascular-glia interaction and breathing control are compromised in PD.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0361-9230 1873-2747
DOI:	10.1016/j.brainresbull.2022.06.011