Purinergic signalling within the Retrotrapezoid Nucleus region: role of breathing control in the temporal lobe epilepsy model

• Grant number: 17/08696-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2017
• End date: February 28, 2021
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Thiago dos Santos Moreira
• Grantee: Milene Rodrigues Malheiros Lima
• Host 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

Breathing control and central chemoreception are regulated by the retrotrapezoid nucleus (RTN), a group of glutamatergic neurons that express the transcription factor Phox2b and are strongly activated by increase in CO2/H+. Cerebral blood flow is highly sensitive to changes in CO2/H+ where an increase in CO2/H+ causes vasodilation and increased blood flow. However, our recent discovery showed that CO2/H+-dependent regulation of vascular tone in the RTN is the opposite to the rest of the cerebral vascular tree, causing vasoconstriction. Our results also suggest that regulation of vascular tone in the RTN contributes functionally to the ventilatory response to CO2. In addition, we also demonstrated that purinergic signaling modulate the CO2/H+-induced dilation, possibly acting through P2 receptors in the RTN. Breathing dysfunctions, as central apnea and reduced sensitivity to PCO2 changes were observed in temporal lobe epilepsy models, being in some cases, correlated with ablation of RTN neurons. However, the role of glia cells, an important source of ATP in RTN region, was evaluated only in hippocampus and amygdala of epilepsy models. Taking into account that (a) RTN showed a special regulation of blood vessels which contribute to chemosensibility, (b) purinergic signaling in RTN contribute to vascular tone and breathing, (c) glia cells are a importance source of ATP into RTN region, and (d) epileptic models showed breathing dysfunction and reduction in central chemosensitivity, this project will intend to analyze the role of purinergic signaling from neurons and glia cells of RTN region to vascular tone of RTN and breathing dysfunction in a temporal lobe epilepsy model.

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TAKAKURA, ANA C.; MALHEIROS-LIMA, MILENE R.; MOREIRA, THIAGO S.. Excitatory and inhibitory modulation of parafacial respiratory neurons in the control of active expiration. Respiratory Physiology & Neurobiology, v. 289, JUL 2021. (17/08696-5, 19/01236-4, 15/23376-1)

MAIA, OCTAVIO A. C.; MALHEIROS-LIMA, MILENE R.; OLIVEIRA, MARIA A.; CASTRO, CLAUDIO L.; MORIYA, HENRIQUE T.; TAVARES-DE-LIMA, WOTHAN; TAKAKURA, ANA C.; MOREIRA, THIAGO S.. Pilocarpine-induced status epilepticus reduces chemosensory control of breathing. Brain Research Bulletin, v. 161, p. 98-105, AUG 2020. (15/23376-1, 16/23281-3, 17/08696-5)

MALHEIROS-LIMA, MILENE R.; ANTUNES, VAGNER R.; TAKAKURA, ANA C.; MOREIRA, THIAGO S.. Hypertension and sympathetic nervous system overactivity rely on the vascular tone of pial vessels of the rostral ventrolateral medulla in spontaneously hypertensive rats. Experimental Physiology, v. 105, n. 1, p. 65-74, JAN 2020. (15/23376-1, 16/23281-3, 16/21991-3, 16/22069-0, 17/08696-5)

MALHEIROS-LIMA, MILENE R.; SILVA, TALITA M.; TAKAKURA, ANA C.; MOREIRA, THIAGO S.. 5 noradrenergic-projecting C1 neurons activate sympathetic and breathing outputs in anaesthetized rat. Experimental Physiology, v. 107, n. 2, DEC 2021. (17/08696-5, 19/01236-4, 15/23376-1)