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

Autor(es)

Amorim, Mateus R. ^{[1, 2]} ; Dergacheva, Olga ^[3] ; Fleury-Curado, Thomaz ^[2] ; Pho, Huy ^[2] ; Freire, Carla ^[2] ; Mendelowitz, David ^[3] ; Branco, Luiz G. S. ^[1] ; Polotsky, Vsevolod Y. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dent Sch Ribeirao Preto, BR-14040904 Ribeirao Preto, SP - Brazil

^[2] Johns Hopkins Univ, Dept Med, Div Pulm & Crit Care Med, Sch Med, Baltimore, MD 21224 - USA

^[3] George Washington Univ, Dept Pharmacol & Physiol, Washington, DC 20037 - USA

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 13 JUL 2021.
• Citações Web of Science: 0

Resumo

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 Lepr(b)-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. (AU)

• Processo FAPESP: 19/13249-3 - O papel da sinalização da leptina no hipotálamo dorsomedial na permeabilidade das vias aéreas superiores durante o sono
• Beneficiário: Mateus Ramos Amorim
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado