Πέμπτη 3 Αυγούστου 2017

Active sleep unmasks apnea and delayed arousal in infant rat pups lacking central serotonin

Sudden Infant Death Syndrome (SIDS), occurring during sleep periods, is highly associated with abnormalities within serotonin (5-HT) neurons, including reduced 5-HT. There is evidence that future SIDS cases experience more apnea and have abnormal arousal from sleep. In rodents, a loss of 5-HT neurons is associated with apnea in early life and, in adulthood, delayed arousal. As the activity of 5-HT neurons changes with vigilance state, we hypothesized that the degree of apnea and delayed arousal displayed by rat pups specifically lacking central 5-HT varies with state. Two week-old tryptophan hydroxylase 2-deficient (TPH2-/-) and wild-type (WT) rat pups were placed in plethysmographic chambers supplied with room air. At the onset of active (AS) or quiet sleep (QS), separate groups of rats were exposed to hypercapnia (5% CO2), or mild hypoxia (~17% O2) or maintained in room air. Upon arousal, rats received room air. Apnea indices and latencies to spontaneous arousal from AS and QS were determined for pups exposed only to room air. Arousal latencies were also calculated for TPH2-/- and WT pups exposed to hypoxia or hypercapnia. Compared to WT, TPH2-/- pups hypoventilated in all states, but were profoundly more apneic solely in AS. TPH2-/- pups had delayed arousal in response to increasing CO2, and AS selectively delayed the arousal of TPH2-/- pups, irrespective of the gas they breathed. Thus, infants who are deficient in CNS 5-HT may be at increased risk for SIDS in active sleep due to increased apnea and delayed arousal compared to quiet sleep.



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