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Participation of respiratory oscillators on the modulation of RVLM presympathetic neurons in offspring from obese dams

Grant number: 19/11696-2
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): August 01, 2019
Effective date (End): April 30, 2020
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Débora Simões de Almeida Colombari
Grantee:Marlusa Karlen Amarante
Supervisor abroad: Jan Marino Ramirez
Home Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Local de pesquisa : University of Washington, United States  
Associated to the scholarship:16/23513-1 - Experimental pathophysiology: role of central mechanisms of the cardiovascular and respiratory control changes induced by experimental Hypertension and Obesity, BP.PD

Abstract

Obesity is associated with the development of pathologies including cardiovascular diseases, hormonal and respiratory dysfunctions. Recently, studies have suggested that gestational obesity may also have an impact on the development of pathologies in offspring. The cardiorespiratory changes observed in the offspring promoted by maternal obesity, as well as the neural mechanisms involved, are the object of study in our laboratory. For this, adult Holtzman rats (250 g) were fed with a high fat diet (HFD - 45% calories from fat) or standard diet for rodents (SD) during the 6 weeks before gestation until the end of lactation. After weaning, the male offspring of group SD (O-SD) and HFD (O-HFD) were fed with standard feed until the day of the experiment (P27-32). Using a decerebrated arterially perfused in situ rat preparation, we found that juvenile O-HFD rats presented active expiration under resting conditions, with increased abdominal activity during late-expiration (late-E) and prolonged hypoglossal pre-inspiratory activity. In addition, O-HFD rats exhibited increased sympathetic activity and a blunted respiratory-sympathetic coupling (due to increased sympathetic activity during expiratory phases - E1 and E2). We observed that this was associated with augmented discharge frequency of some RVLM presympathetic neurons during expiratory phase (mostly late-E phase). In order to explain the increase in sympathetic activity of O-HFD rats, we hypothesize that the coupling between RVLM and conditional oscillators (preBötC, PICo and of pFRG) is strengthened, enhancing the excitatory drive to sympathetic neurons during E1 and E2 phases. However, we need first to elucidate how these respiratory compartments interact with RVLM under resting conditions. In other words, we still do not know how the three respiratory oscillators interact with and modify the activity of RVLM neurons. Thus, the aim of this project is to investigate how and when the respiratory oscillators (pre-BötC, pFRG and PICo) interact with the neurons responsible for the generation of sympathetic activity in the O-HFD. To achieve these goals, we will record RVLM presympathetic neurons (IML-projecting neurons or C1 neurons) in transverse slices and/or in situ preparations from O-SD and O-HFD transgenic mice and using optogenetic approaches we will stimulate / inhibit neuronal populations of interest (preBötC, PiCo and pFRG).