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Role of astrocytes in inhibitory transmission in the NTS chemoreflex neural pathways of rats exposed hypoxia maintained

Grant number: 19/21276-0
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): January 01, 2020
Effective date (End): February 28, 2022
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Benedito Honorio Machado
Grantee:Júlio César Pascoaloti de Lima
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:18/15957-2 - Astrocytic modulation on brainstem neurons involved with generation and control of sympathetic and respiratory activities in rodents submitted to hypoxia, AP.TEM


In situations that occur decreases in arterial blood O2 pressure (hypoxia), there is activation of peripheral chemoreflex, which induces autonomic and respiratory reflex responses to reestablish O2 pressure. The chemoreflex neural pathways involve the activation of neurons and astrocytes located in the tripartite synapses of the solitary tract nucleus (NTS) and are modulated by excitatory and inhibitory neurotransmitters. Regarding the excitatory transmission of chemoreflex, the involvement of glutamate has been well described in the literature. Although the main inhibitory neurotransmitter of NTS is the inhibitory amino acid GABA, its participation in the chemoreflex sympathetic and respiratory responses has been little explored. In this project, we are evaluating through the whole-cell patch-clamp technique whether the sustained hypoxia (HM) model affects GABAergic (spontaneous and stimulated) neurotransmission in intermediate and caudal NTS neurons involved with the chemoreflex neural pathways and protrude into the ventral brainstem region (VLM). Our initial results show that MH decreases TS-eIPSCs of NTS-VLM neurons without changing the rise-time and decay-time parameters. This change appears to be due to a change in the presynaptic component because parameter 1/CV2 is decreased in MH animals, but there are no changes in the short-term depression parameter, suggesting that the NTS of HM rats may have a lower number of active GABAergic synapses. We also observed a lower frequency of sIPSCs with no change in amplitude and half-widths. Rostral NTS-VLM neurons, which are not involved with the chemoreflex neural pathways, showed no alterations in TS-eIPSCs, demonstrating that these neurons are not modified by hypoxia. This set of results show that MH causes changes in GABAergic neurotransmission of NTS neurons involved with chemoreflex neural pathways. The next steps of the project intend to investigate if the observed changes in GABAergic currents are due to post synaptic and/or presynaptic alterations, what is the role of astrocytes in the modulation of GABAergic currents of these neurons, what are the possible morphological alterations that hypoxia can induce in these neurons involved in the chemoreflex pathway. (AU)

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Scientific publications
(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)
PASCOALOTI-LIMA, JULIO C.; MACHADO, BENEDITO H.; ACCORSI-MENDONCA, DANIELA. Sustained Hypoxia Reduces GABAergic Modulation on NTS Neurons Sending Projections to Ventral Medulla of Rats. Neuroscience, v. 457, p. 1-11, . (18/15957-2, 19/21276-0)
PASCOALOTI-LIMA, JULIO C.; MACHADO, BENEDITO H.; ACCORSI-MENDONCA, DANIELA. Sustained Hypoxia Reduces GABAergic Modulation on NTS Neurons Sending Projections to Ventral Medulla of Rats (Retracted article. See vol. 493, pg. 120, 2022). Neuroscience, v. 457, p. 11-pg., . (18/15957-2, 19/21276-0)

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