A Short-Term Fasting in Neonates Induces Breathing Instability and Epigenetic Modification in the Carotid Body.

The respiratory control system is not fully developed in newborn, and data suggest that adequate nutrition is important for the development of the respiratory control system. Infants need to be fed every 2-4 h to maintain appropriate energy levels, but a skip of feeding can occur due to social economical reasons or mild sickness of infants. Here, we asked questions if a short-term fasting (1) alters carotid body (CB) chemoreceptor activity and integrated function of the respiratory control system; (2) causes epigenetic modification within the respiratory control system. Mouse pups (<P14) were fasted for 3-6 h. Breathing became irregular and slow. The number and duration of apnea increased. Ventilatory response to hypoxia was also depressed even after the pups were returned to own dams. These effects were more prominent when the pups were younger and fasting time was longer. The hypoxic response of the carotid sinus nerve activity appeared to be depressed after fasting. Moreover, fasting increased global 5mC and 5-hmC content in DNA isolated from the CB but not DNA in the superior cervical ganglion (SCG). Methylation specific PCR (MSPCR) revealed that fasting increased methylation of leptin and socs3 genes. The results suggest fasting inhibits CB activity leading to hypoventilation, and low glucose does not compensate the low CB activity. Epigenetic effect on CB function/activity may be related to the prolonged effect of fasting on ventilation.