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Regulation of blood flow in the ventrolateral surface of the medulla in animal a model of Parkinson's Disease

Grant number: 19/09323-3
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): June 01, 2019
Effective date (End): May 31, 2021
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Ana Carolina Thomaz Takakura
Grantee:Luiz Marcelo Oliveira Santos
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:15/23376-1 - Retrotrapezoid nucleus, respiratory chemosensitivity and breathing automaticity, AP.TEM

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder known for its progressive loss of dopaminergic neurons in the compact portion of the substantia nigra (SNpc). Much less known, although clinically very important, are the damaging effects on respiration associated with PD. Studies using the 6-hydroxydopamine (6-OHDA) model in rats revealed reduced respiratory rate (fR), central chemorreflex impairment and decreased immunoreactivity for the Phox2b transcription factor in the retrotrapezoid nucleus (RTN). RTN is a group of glutamatergic neurons that plays an important role in the central chemoreception process and in respiratory automatism. Recent studies have demonstrated that the blood flow in the ventrolateral region of the medulla is decreased in a situation of high CO2 levels; This characteristic is attributed to the participation of the astrocytes located in this region and their probable release of neurotransmitters such as ATP and glutamate in the regulation of blood flow. From these evidences, it becomes important to investigate the role of astrocyte cells located in the region of the RTN in the blood vessel tonus in the experimental model of PD. The experiments developed in this project seek to test whether in the experimental model of PD, astrocytes and neurotransmitters released by this group of cells are more influential in regulating blood flow in the ventrolateral region of the medulla in rats through hypercapnia, electrophysiological experiments associated with pharmacology and immunohistochemistry techniques.