Prenatal diazepam exposure alters respiratory control system and GABAA and adenosine receptor gene expression in newborn rats
| Autor: | Stéphanie Guénin, Yolande Perrin, Nicole Larnicol, Gérard Hilaire, Nathalie Picard |
|---|---|
| Přispěvatelé: | Génie Enzymatique et Cellulaire (GEC), Université de Technologie de Compiègne (UTC)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Respiratory rate Receptor Adenosine A2A medicine.drug_class Biology Hypnotic Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Pregnancy Internal medicine medicine Tidal Volume Animals RNA Messenger Respiratory system GABA Modulators Hypoxia Tidal volume 030304 developmental biology 0303 health sciences Fetus Diazepam GABAA receptor Receptor Adenosine A1 Respiration digestive oral and skin physiology Receptors Purinergic P1 Gene Expression Regulation Developmental Respiratory Center Receptors GABA-A Adenosine receptor 3. Good health Rats Endocrinology Animals Newborn Prenatal Exposure Delayed Effects Pediatrics Perinatology and Child Health Respiratory Mechanics Female 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Pediatric Research Pediatric Research, Nature Publishing Group, 2008, 64 (1), pp.44-49 |
| ISSN: | 0031-3998 1530-0447 |
| Popis: | International audience; In experimental animals, prenatal diazepam exposure has clearly been associated with behavioral disturbances. Its impact on newborn breathing has not been documented despite potential deleterious consequences for later brain development. We addressed this issue in neonatal rats (0-2 d) born from dams, which consumed 2 mg/kg/d diazepam via drinking fluid throughout gestation. In vivo, prenatal diazepam exposure significantly altered the normoxic-breathing pattern, lowering breathing frequency (105 vs. 125 breaths/min) and increasing tidal volume (16.2 vs. 12.7 mL/kg), and the ventilatory response to hypoxia, inducing an immediate and marked decrease in tidal volume (-30%) absent in controls. In vitro, prenatal diazepam exposure significantly increased the respiratory-like frequency produced by pontomedullary and medullary preparations (+38% and +19%, respectively) and altered the respiratory-like response to application of nonoxygenated superfusate. Both in vivo and in vitro, the recovery from oxygen deprivation challenges was delayed by prenatal diazepam exposure. Finally, real-time PCR showed that prenatal diazepam exposure affected mRNA levels of alpha1 and alpha2 GABAA receptor subunits and of A1 and A2A adenosine receptors in the brainstem. These mRNA changes, which are region-specific, suggest that prenatal diazepam exposure interferes with developmental events whose impact on the respiratory system maturation deserves further studies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|