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

Author(s)

Oliveira, Luiz M. ; Fernandes-Junior, Silvio A. ; Cabral, Lais M. C. ; Miranda, Nicole C. S. ; Czeisler, Catherine M. ; Otero, Jose J. ; Moreira, Thiago S. ; Takakura, Ana C.

• Document type: Journal article
• Source: Brain Research Bulletin; v. 187, p. 17-pg., 2022-07-12.

Abstract

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 neuro-logical 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 (FiCO(2) = 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 proteo-mic 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. (AU)

• FAPESP's process: 15/23376-1 - Retrotrapezoid nucleus, respiratory chemosensitivity and breathing automaticity
• Grantee: Thiago dos Santos Moreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/11165-1 - Respiratory deficit in an experimental model of Parkinson's Disease may be associated with changes in the Phox2b gene at the level of the ventrolateral medulla
• Grantee: Silvio de Araujo Fernandes Junior
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 19/09323-3 - Regulation of blood flow in the ventrolateral surface of the medulla in animal a model of Parkinson's disease
• Grantee: Luiz Marcelo Oliveira Santos
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/20695-6 - Analysis of the selective activation of medullary neurons in an experimental model of Parkinson's Disease: a time study of the possible mechanisms for restoration of respiratory function
• Grantee: Silvio de Araujo Fernandes Junior
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/01236-4 - Effects of pharmacological and non-pharmacological treatments on respiratory changes observed in a murine model of Parkinson's disease
• Grantee: Ana Carolina Takakura Moreira
• Support Opportunities: Regular Research Grants