title: Involvement of adenosinergic A1 systems in the occurrence of respiratory perturbations encountered in newborns following an in utero caffeine exposure. a study on brainstem-spinal cord preparations isolated from newborn rats.
abstract: Involvement of adenosinergic A1 systems in the occurrence of respiratory perturbations encountered in newborns following an in utero caffeine exposure has been investigated on pontomedullary-spinal cord, caudal pons-medullary-spinal cord and medullary-spinal cord preparations isolated from newborn rats. According to the drinking fluid of dams (tap water or 0.02% caffeine), two groups of preparations were distinguished, no-caffeine and caffeine. In the no-caffeine group, adenosine A1 receptor activation induces a decrease in respiratory frequency (Rf) in caudal pons-medullary-spinal cord and medullary-spinal cord preparations whereas, in presence of the rostral pons, an increase is observed. A parallel Fos detection indicates that this discrepancy may be due to the excitatory action of the medial parabrachial nucleus at the rostral pontine level that surpasses inhibitory influence of the adenosine A1 receptor activation at the medullary level particularly in the ventrolateral reticular nucleus of the medulla. In caffeine group, an increase in the baseline Rf in presence of the pons and no change in medullary-spinal cord preparations have been observed. Depending on Fos detection, we assume that the medial parabrachial nucleus is the main region involved in the exaggeration of Rf. Moreover, adenosine A1 receptor activation was modified by in utero caffeine exposure with an overcharge of the Rf increase in pontomedullary-spinal cord preparations and an exaggeration of the Rf decrease in medullary-spinal cord preparations. Based on Fos detection, we link the overcharge in Rf of pontomedullary spinal cord preparations to an increase in the medial parabrachial nucleus neuronal activity. Similarly, exaggeration of Rf decrease observed without the pons is linked with a decrease in activity of the ventrolateral reticular neurons. This study brings evidence for the involvement of adenosinergic A1 systems in the occurrence of respiratory perturbations in newborns following in utero caffeine exposure and the importance of rostral pons in the adenosinergic A1 modulation of the respiratory control.
authors.affiliation: Laboratoire de Dysrégulations Métaboliques Acquises et génétiques EA 2088-EA 2629, Faculté de Médecine, 3 rue des Louvels, 80036 Amiens cedex 1, France.
authors.forename: F
authors.initials: F
authors.lastname: Saadani-Makki
authors.forename: A
authors.initials: A
authors.lastname: Frugière
authors.forename: F
authors.initials: F
authors.lastname: Gros
authors.forename: S
authors.initials: S
authors.lastname: Gaytan
authors.forename: L
authors.initials: L
authors.lastname: Bodineau
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002110:Caffeine / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008526:Medulla Oblongata / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D011149:Pons / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D043682:Receptor, Adenosine A1 / Q000187:drug effects* / Q000378:metabolism; D012125:Respiratory Center / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D012143:Respiratory Physiological Phenomena / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D014970:Xanthines / Q000494:pharmacology
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D043682:Receptor, Adenosine A1; D014970:Xanthines; C047235:N-(1-methyl-2-phenylethyl)adenosine; D002110:Caffeine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine