Related Experiment Videos
Perinatal respiratory control and its modulation by adenosine and caffeine in the rat
Eric Herlenius1, Ulrika Adén, Lie Qi Tang
1Department of Woman and Child Health, Karolinska Hospital, Stockholm, Sweden. Eric.Herlenius@dsg.ki.se
Insights
Respiratory rhythm generation in fetal rats is modulated by adenosine A(1) receptors. Maternal caffeine intake enhanced respiratory network activity and pontine inhibition, without altering A(1) receptor expression.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Respiratory rhythm generation is crucial for survival and develops during the perinatal period.
- Adenosine A(1) receptors are known modulators of neuronal activity.
- Maternal factors, such as caffeine consumption, can influence fetal development.
Purpose of the Study:
- To investigate the perinatal development of respiratory rhythm generation in rats.
- To examine the modulatory effects of adenosinergic drugs on respiratory networks.
- To assess the impact of maternal caffeine exposure on fetal respiratory development.
Main Methods:
- Used an in vitro brain stem-spinal cord preparation from embryonic day 18 (E18) to postnatal day 3 (P3) rats.
- Administered adenosine A(1)-receptor agonist (R-PIA) and antagonist (theophylline) to assess receptor function.
- Studied adenosine A(1)-mRNA and receptor expression using molecular and biochemical techniques.
Main Results:
- Respiratory rhythm generation and pontine inhibition were evident by E18.
- Adenosine A(1)-receptor agonist (R-PIA) reduced respiratory frequency in an age-dependent manner, reversible by theophylline.
- Maternal caffeine exposure led to more pronounced pontine inhibition and increased respiratory frequency upon pontine removal, without altering A(1) receptor expression.
Conclusions:
- Respiration is modulated by adenosine A(1) receptors in the medulla oblongata during the fetal period.
- Maternal caffeine intake during gestation enhances pontine inhibition and activity of respiratory rhythm-generating networks.
- These effects occur without significant changes in A(1)-receptor number or mRNA expression.
Abstract:
The perinatal development of respiratory rhythm generation and its modulation by adenosinergic drugs have been examined in rats from embryonic d 18 (E18) to postnatal d 3 using an in vitro brain stem-spinal cord preparation. Generation of rhythmic respiratory activity in the medulla oblongata and inhibition of this activity by pontine structures were evident on E18. The adenosine A(1)-receptor agonist, N(6)-(2-phenylisopropyl) adenosine, R (-) isomer (R-PIA) (1 microM), induced an age-dependent reduction of respiratory frequency that could be reversed by the adenosine antagonist theophylline (55 microM). The effect of R-PIA was reduced 24 h after birth compared with E21 and 2 h postnatal age. In preparations from pups that had been exposed to a low dose of caffeine (0.3 g/L in drinking water to dams), pontine inhibition of respiratory rhythm generation in the medulla was more pronounced. When the pons was removed, the respiratory frequency was higher than in the control group. Adenosine A(1)-mRNA and A(1)-receptor development in pons and medulla were studied, and by E18, mRNA, receptor protein, and functional coupling to G-proteins were confirmed using guanylyl-5'-O-(gamma-[(35)S]thio)-triphosphate binding. There were no major changes in receptor numbers or distribution of A(1) receptors or mRNA in rat pups subjected to caffeine exposure. We conclude that respiration is already modulated by adenosine A(1) receptors at the level of the medulla oblongata in the fetal period in an age-dependent manner. Furthermore, long-term maternal caffeine intake during gestation seems to increase the pontine inhibition of, and the activity of, respiratory rhythm-generating neuronal networks in medulla oblongata without detectable changes in expression of A(1)-receptor number or A(1)-receptor mRNA.