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2 results on '"Thomaz Fleury Curado"'

1. The Effect of DREADD Activation of Leptin Receptor Positive Neurons in the Nucleus of the Solitary Tract on Sleep Disordered Breathing

Author

Mateus R. Amorim, Olga Dergacheva, Thomaz Fleury-Curado, Huy Pho, Carla Freire, David Mendelowitz, Luiz G. S. Branco, and Vsevolod Y. Polotsky

Subjects
obstructive sleep apnea, chemogenetics, upper airway dysfunction, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Obstructive sleep apnea (OSA) is recurrent obstruction of the upper airway due to the loss of upper airway muscle tone during sleep. OSA is highly prevalent, especially in obesity. There is no pharmacotherapy for OSA. Previous studies have demonstrated the role of leptin, an adipose-tissue-produced hormone, as a potent respiratory stimulant. Leptin signaling via a long functional isoform of leptin receptor, LEPRb, in the nucleus of the solitary tract (NTS), has been implicated in control of breathing. We hypothesized that leptin acts on LEPRb positive neurons in the NTS to increase ventilation and maintain upper airway patency during sleep in obese mice. We expressed designer receptors exclusively activated by designer drugs (DREADD) selectively in the LEPRb positive neurons of the NTS of Leprb-Cre-GFP mice with diet-induced obesity (DIO) and examined the effect of DREADD ligand, J60, on tongue muscle activity and breathing during sleep. J60 was a potent activator of LEPRb positive NTS neurons, but did not stimulate breathing or upper airway muscles during NREM and REM sleep. We conclude that, in DIO mice, the stimulating effects of leptin on breathing during sleep are independent of LEPRb signaling in the NTS.

Published
2021
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2. The Role of Animal Models in Developing Pharmacotherapy for Obstructive Sleep Apnea

Author

Thomaz Fleury Curado, Vsevolod Y. Polotsky, Jonathan C. Jun, Lenise Jihe Kim, and Carla Freire

Subjects
medicine.medical_specialty, medicine.medical_treatment, lcsh:Medicine, loop gain, Review, Disease, Poor adherence, pharmacotherapy, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, stomatognathic system, Low arousal theory, medicine, Continuous positive airway pressure, Intensive care medicine, obstructive sleep apnea, upper airway anatomy, business.industry, lcsh:R, General Medicine, neuromuscular response, medicine.disease, animal models, nervous system diseases, respiratory tract diseases, 3. Good health, Obstructive sleep apnea, arousal threshold, 030228 respiratory system, Respiratory control, Airway, business, 030217 neurology & neurosurgery
Abstract

Obstructive sleep apnea (OSA) is a highly prevalent disease characterized by recurrent closure of the upper airway during sleep. It has a complex pathophysiology involving four main phenotypes. An abnormal upper airway anatomy is the key factor that predisposes to sleep-related collapse of the pharynx, but it may not be sufficient for OSA development. Non-anatomical traits, including (1) a compromised neuromuscular response of the upper airway to obstruction, (2) an unstable respiratory control (high loop gain), and (3) a low arousal threshold, predict the development of OSA in association with anatomical abnormalities. Current therapies for OSA, such as continuous positive airway pressure (CPAP) and oral appliances, have poor adherence or variable efficacy among patients. The search for novel therapeutic approaches for OSA, including pharmacological agents, has been pursued over the past years. New insights into OSA pharmacotherapy have been provided by preclinical studies, which highlight the importance of appropriate use of animal models of OSA, their applicability, and limitations. In the present review, we discuss potential pharmacological targets for OSA discovered using animal models.

Published
2019

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