Friday, January 13, 2012

Neonatal Hypoxia and Sleep

cross posted at


Unfortunately this paper does not report any data on sleep. Too bad, it would seem a natural (and interesting) complement to the paper. The Authors show that neonatal hypoxia lead to long lasting vegetative dysregulation,  especially in ventilation and arterial pressure, by mean of DNA methilation. I'm not here discussing the genetic part (very intriguing), but I would like to comment on the physiology used in the paper.

1) To assess to presence of breathing dysregulation in adulthood, animal exposed to hypoxia bout in young age were housed for 2 hours in a whole body plethysmogrphy (from 9:00 to 11:00) . Results: the hypoxia exposed animals have more apnea episodes than the control. Now the interesting question is: were these animal asleep (remember that rats are nocturnal animals, so they sleep during the day)?  Rats spontaneously show episode of central apnea during REM sleep, and it would have been very interesting, especially for the point this paper try to make, to show if the apnea episodes were REM sleep related.

2) Arterial pressure was measured by tail cuff in the same time window (9:00 - 11:00). I am just very curious on what would a 24h telemetric arterial pressure recording have shown. Arterial pressure (and heart rate) is interestingly modulated by sleep, showing different features in different part of the sleep-wake cycle (i.e. dipping vs non-dipping phenotype, or arterial pressure surges in REM sleep) and would have been extremely interesting to see the effects of neonatal hypoxia exposure on such phenomena.

3) No thermoregulatory / metabolic measure. Is the altered chemoreflex somehow affecting also thermoregulation or metabolism? We don't know (yet).

In conclusion, I hope the Authors would continue to analyze this very interesting model, maybe with just a little bit more physiology (that seems to be disappearing from the abundance of genetic / biochemical experiments conducted today) 

Epigenetic regulation of hypoxic sensing disrupts cardiorespiratory homeostasis.:

Proc Natl Acad Sci U S A. 2012 Jan 9;

Authors: Nanduri J, Makarenko V, Reddy VD, Yuan G, Pawar A, Wang N, Khan SA, Zhang X, Kinsman B, Peng YJ, Kumar GK, Fox AP, Godley LA, Semenza GL, Prabhakar NR

Recurrent apnea with intermittent hypoxia is a major clinical problem in preterm infants. Recent studies, although limited, showed that adults who were born preterm exhibit increased incidence of sleep-disordered breathing and hypertension, suggesting that apnea of prematurity predisposes to autonomic dysfunction in adulthood. Here, we demonstrate that adult rats that were exposed to intermittent hypoxia as neonates exhibit exaggerated responses to hypoxia by the carotid body and adrenal chromaffin cells, which regulate cardio-respiratory function, resulting in irregular breathing with apneas and hypertension. The enhanced hypoxic sensitivity was associated with elevated oxidative stress, decreased expression of genes encoding antioxidant enzymes, and increased expression of pro-oxidant enzymes. Decreased expression of the Sod2 gene, which encodes the antioxidant enzyme superoxide dismutase 2, was associated with DNA hypermethylation of a single CpG dinucleotide close to the transcription start site. Treating neonatal rats with decitabine, an inhibitor of DNA methylation, during intermittent hypoxia exposure prevented oxidative stress, enhanced hypoxic sensitivity, and autonomic dysfunction. These findings implicate a hitherto uncharacterized role for DNA methylation in mediating neonatal programming of hypoxic sensitivity and the ensuing autonomic dysfunction in adulthood.

PMID: 22232674 [PubMed - as supplied by publisher]