| Texto completo | |
| Autor(es): |
Moreira, Thiago S.
;
Burgraff, Nicholas J.
;
Takakura, Ana C.
;
Oliveira, Luiz M.
;
de Araujo, Emmanuel V.
;
Guan, Steven
;
Ramirez, Jan-Marino
Número total de Autores: 7
|
| Tipo de documento: | Artigo Científico |
| Fonte: | AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY; v. 329, n. 3, p. 19-pg., 2025-09-23. |
| Resumo | |
The primary cause of death from opioid overdose is opioid-induced respiratory depression (OIRD), characterized by severe suppression of respiratory rate, destabilized breathing patterns, hypercapnia, and heightened risk of apnea. The retrotrapezoid nucleus (RTN), a critical chemosensitive brainstem region in the rostral ventrolateral medullary reticular formation, contains Phox2b +/neuromedin-B (Nmb) propriobulbar neurons. These neurons, stimulated by CO2/H+, regulate breathing to prevent respiratory acidosis. Since the RTN shows limited expression of opioid receptors, we expected that opioid-induced hypoventilation should activate these neurons to restore ventilation and stabilize arterial blood gases. However, the ability of the RTN to stimulate ventilation during OIRD has never been tested. We used optogenetic and pharmacogenetic approaches, to activate and inhibit RTN Phox2b(+)/Nmb(+) neurons before and after fentanyl administration. As expected, fentanyl (500 lg/kg ip) suppressed respiratory rate and destabilized breathing. Before fentanyl, optogenetic stimulation of Phox2b+/Nmb+ or chemogenetic inhibition of Nmb (+) cells increased and decreased breathing activity, respectively. Surprisingly, optogenetic stimulation after fentanyl administration caused a significantly greater increase in breathing activity compared with prefentanyl levels. In contrast, chemogenetic inhibition of RTN Nmb neurons caused profound hypoventilation and breathing instability after fentanyl. The results suggest that fentanyl does not inhibit the ability of Phox2b(+)/Nmb(+)cells within the RTN region to stimulate breathing. Thus, this study highlights the potential of stimulating RTN neurons as a possible therapeutic approach to restore respiratory function in cases of opioid-induced respiratory depression (OIRD). (AU) | |
| Processo FAPESP: | 22/09734-6 - Mecanismos de fisiologia celular, molecular e integrativa subjacentes à depressão respiratória induzida por opióides |
| Beneficiário: | Thiago dos Santos Moreira |
| Modalidade de apoio: | Bolsas no Exterior - Pesquisa |
| Processo FAPESP: | 21/05299-0 - Controle do ritmo e da quimiossensibilidade respiratória pelo tronco encefálico: aspectos moleculares, celulares, fisiológicos e patológicos |
| Beneficiário: | Thiago dos Santos Moreira |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 22/07705-9 - Alterações respiratórias associadas ao sono observadas na Doença de Parkinson |
| Beneficiário: | Ana Carolina Takakura Moreira |
| Modalidade de apoio: | Bolsas no Exterior - Pesquisa |
| Processo FAPESP: | 21/09768-5 - Influências do dimorfismo sexual, inflamação e sono nas alterações respiratórias observadas na Doença de Parkinson |
| Beneficiário: | Ana Carolina Takakura Moreira |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |