Chemogenetic stimulation of the hypoglossal neurons improves upper airway patency

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art_CURADO_Chemogenetic_stimulation_of_the_hypoglossal_neurons_improves_upper_2017.PDF (943.75 KB)
Citações na Scopus
31
Tipo de produção
article
Data de publicação
2017
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
NATURE PUBLISHING GROUP
Autores
FISHBEIN, Kenneth
Huy Pho
BRENNICK, Michael
DERGACHEVA, Olga
PHAM, Luu V.
LADENHEIM, Ellen E.
SPENCER, Richard
MENDELOWITZ, David
Citação
SCIENTIFIC REPORTS, v.7, article ID 44392, 7p, 2017
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction during sleep. OSA leads to high cardiovascular morbidity and mortality. The pathogenesis of OSA has been linked to a defect in neuromuscular control of the pharynx. There is no effective pharmacotherapy for OSA. The objective of this study was to determine whether upper airway patency can be improved using chemogenetic approach by deploying designer receptors exclusively activated by designer drug (DREADD) in the hypoglossal motorneurons. DREADD (rAAV5-hSyn-hM3(Gq)-mCherry) and control virus (rAAV5-hSyn-EGFP) were stereotactically administered to the hypoglossal nucleus of C57BL/6J mice. In 6-8 weeks genioglossus EMG and dynamic MRI of the upper airway were performed before and after administration of the DREADD ligand clozapine-N-oxide (CNO) or vehicle (saline). In DREADD-treated mice, CNO activated the genioglossus muscle and markedly dilated the pharynx, whereas saline had no effect. Control virus treated mice showed no effect of CNO. Our results suggest that chemogenetic approach can be considered as a treatment option for OSA and other motorneuron disorders.
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URI
https://observatorio.fm.usp.br/handle/OPI/20094
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MOF
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/32