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Orexin Neurons Contribute to Central Modulation of Respiratory Drive by Progestins on ex vivo Newborn Rodent Preparations.
Front Physiol 2019; 10:1200FP

Abstract

Dysfunction of central respiratory CO2/H+ chemosensitivity is a pivotal factor that elicits deep hypoventilation in patients suffering from central hypoventilation syndromes. No pharmacological treatment is currently available. The progestin desogestrel has been suggested to allow recovery of respiratory response to CO2/H+ in patients suffering from central hypoventilation, but except the fact that supramedullary regions may be involved, mechanisms are still unknown. Here, we tested in neonates whether orexin systems contribute to desogestrel's central effects on respiratory function. Using isolated ex vivo central nervous system preparations from newborn rats, we show orexin and almorexant, an antagonist of orexin receptors, supressed strengthening of the increase in respiratory frequency induced by prolonged metabolic acidosis under exposure to etonogestrel, the active metabolite of desogestrel. In parallel, almorexant suppressed the increase and enhanced increase in c-fos expression in respiratory-related brainstem structures induced by etonogestrel. These results suggest orexin signalisation is a key component of acidosis reinforcement of respiratory drive by etonogestrel in neonates. Although stage of development used is different as that for progestin clinical observations, presents results provide clues about conditions under which desogestrel or etonogestrel may enhance ventilation in patients suffering from central hypoventilation syndromes.

Authors+Show Affiliations

Institut National de la Santé et de la Recherche Médicale, UMR_S1158 Neurophysiologie Respiratoire Expérimentale et Clinique, Sorbonne Université, Paris, France.Institut National de la Santé et de la Recherche Médicale, UMR_S1158 Neurophysiologie Respiratoire Expérimentale et Clinique, Sorbonne Université, Paris, France.Institut National de la Santé et de la Recherche Médicale, UMR_S1158 Neurophysiologie Respiratoire Expérimentale et Clinique, Sorbonne Université, Paris, France.Institut National de la Santé et de la Recherche Médicale, UMR_S1158 Neurophysiologie Respiratoire Expérimentale et Clinique, Sorbonne Université, Paris, France.Institut National de la Santé et de la Recherche Médicale, UMR_S1158 Neurophysiologie Respiratoire Expérimentale et Clinique, Sorbonne Université, Paris, France.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31611806

Citation

Loiseau, Camille, et al. "Orexin Neurons Contribute to Central Modulation of Respiratory Drive By Progestins On Ex Vivo Newborn Rodent Preparations." Frontiers in Physiology, vol. 10, 2019, p. 1200.
Loiseau C, Casciato A, Barka B, et al. Orexin Neurons Contribute to Central Modulation of Respiratory Drive by Progestins on ex vivo Newborn Rodent Preparations. Front Physiol. 2019;10:1200.
Loiseau, C., Casciato, A., Barka, B., Cayetanot, F., & Bodineau, L. (2019). Orexin Neurons Contribute to Central Modulation of Respiratory Drive by Progestins on ex vivo Newborn Rodent Preparations. Frontiers in Physiology, 10, p. 1200. doi:10.3389/fphys.2019.01200.
Loiseau C, et al. Orexin Neurons Contribute to Central Modulation of Respiratory Drive By Progestins On Ex Vivo Newborn Rodent Preparations. Front Physiol. 2019;10:1200. PubMed PMID: 31611806.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Orexin Neurons Contribute to Central Modulation of Respiratory Drive by Progestins on ex vivo Newborn Rodent Preparations. AU - Loiseau,Camille, AU - Casciato,Alexis, AU - Barka,Besma, AU - Cayetanot,Florence, AU - Bodineau,Laurence, Y1 - 2019/09/27/ PY - 2019/06/07/received PY - 2019/09/03/accepted PY - 2019/10/16/entrez PY - 2019/10/16/pubmed PY - 2019/10/16/medline KW - CO2/H+ chemosensitivity KW - congenital central hypoventilation syndrome KW - etonogestrel KW - ex vivo central nervous system preparation KW - orexin KW - progestin SP - 1200 EP - 1200 JF - Frontiers in physiology JO - Front Physiol VL - 10 N2 - Dysfunction of central respiratory CO2/H+ chemosensitivity is a pivotal factor that elicits deep hypoventilation in patients suffering from central hypoventilation syndromes. No pharmacological treatment is currently available. The progestin desogestrel has been suggested to allow recovery of respiratory response to CO2/H+ in patients suffering from central hypoventilation, but except the fact that supramedullary regions may be involved, mechanisms are still unknown. Here, we tested in neonates whether orexin systems contribute to desogestrel's central effects on respiratory function. Using isolated ex vivo central nervous system preparations from newborn rats, we show orexin and almorexant, an antagonist of orexin receptors, supressed strengthening of the increase in respiratory frequency induced by prolonged metabolic acidosis under exposure to etonogestrel, the active metabolite of desogestrel. In parallel, almorexant suppressed the increase and enhanced increase in c-fos expression in respiratory-related brainstem structures induced by etonogestrel. These results suggest orexin signalisation is a key component of acidosis reinforcement of respiratory drive by etonogestrel in neonates. Although stage of development used is different as that for progestin clinical observations, presents results provide clues about conditions under which desogestrel or etonogestrel may enhance ventilation in patients suffering from central hypoventilation syndromes. SN - 1664-042X UR - https://www.unboundmedicine.com/medline/citation/31611806/Orexin_Neurons_Contribute_to_Central_Modulation_of_Respiratory_Drive_by_Progestins_on_ex_vivo_Newborn_Rodent_Preparations L2 - https://doi.org/10.3389/fphys.2019.01200 DB - PRIME DP - Unbound Medicine ER -