Consequences of in utero caffeine exposure on respiratory output in normoxic and hypoxic conditions and related changes of Fos expression: a study on brainstem-spinal cord preparations isolated from newborn rats.
Several aspects of the central regulation of respiratory control have been investigated on brainstem-spinal cord preparations isolated from newborn rats whose dam was given 0.02% caffeine in water as drinking fluid during the whole period of pregnancy. Analysis of the central respiratory drive estimated by the recording of C4 ventral root activity was correlated to Fos ponto-medullary expression. Under normoxic conditions, preparations obtained from the caffeine-treated group of animals displayed a higher respiratory frequency than observed in the control group (9.2 +/- 0.5 versus 7.2 +/- 0.6 burst/min). A parallel Fos detection tends to indicate that the changes of the respiratory rhythm may be due to a decrease in neuronal activity of medullary structures such as the ventrolateral subdivision of the solitary tract, the area postrema, and the nucleus raphe obscurus. Under hypoxic conditions, the preparations displayed a typical hypoxic respiratory depression associated with changes in the medullary Fos expression pattern. In addition, the hypoxic respiratory depression is clearly emphasized after in utero exposure to caffeine and coincides with an increased Fos expression in the area postrema and nucleus raphe obscurus, two structures in which it is not increased in the absence of caffeine. Taken together, these results support the idea that in utero caffeine exposure could affect central respiratory control.
Bodineau
Laurence
L
Laboratoire Environnement Toxique Périnatal et Adaptations Physiologiques et Comportementales, EA 2088, Faculté de Médecine, 3 rue des Louvels, 80036 Amiens cedex 1, France. Laurence.Bodineau@sa.u-picardie.fr
Cayetanot
Florence
F
Sådani-Makki
Fadoua
F
Bach
Véronique
V
Gros
Françoise
F
Lebleu
Aurélia
A
Collin
Thibault
T
Frugière
Alain
A
D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D002110:Caffeine / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000097:blood / Q000134:cerebrospinal fluid; D004594:Electrophysiology; D005260:Female; D002534:Hypoxia, Brain / Q000503:physiopathology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008526:Medulla Oblongata / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D011149:Pons / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012125:Respiratory Center / Q000187:drug effects / Q000378:metabolism; D013116:Spinal Cord / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D014599:Uterus / Q000098:blood supply
D016760:Proto-Oncogene Proteins c-fos; D002245:Carbon Dioxide; D002110:Caffeine