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

摘要

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 pontomedullary 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.Abbreviations: ∫burst, amplitude of the integrated C4 burst activity; AP, area postrema cNTS, commissural subnuclei of the nucleus of the solitary tract; vlNTS, ventrolateral subnuclei of the nucleus of the solitary tract; HRD, hypoxic respiratory depression; PBS, phosphate buffer saline; VLM, ventrolateral reticular nucleus of the medulla; Rf, respiratory frequency; ROb nucleus raphe obscurus FLI, Fos-like immunohistochemistry; RTN, retrotrapezoid nucleus