Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 (QS) sleep, 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 indexes 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 with 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 AS because of increased apnea and delayed arousal compared with QS.NEW & NOTEWORTHY Sudden infant death syndrome (SIDS) occurs during sleep and is associated with central serotonin (5-HT) deficiency. We report that rat pups deficient in central 5-HT (TPH2-/-) are profoundly more apneic in active sleep (AS) but not quiet sleep (QS). Unlike control pups, the arousal of TPH2-/- pups in air, CO2, and hypoxia was delayed in AS compared with QS. Thus for infants deficient in central 5-HT, the risk of SIDS may be higher in AS than in QS.
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PMID:Active sleep unmasks apnea and delayed arousal in infant rat pups lacking central serotonin. 2877 68

We examined the impact of serotonin (5-HT) on the frequency and duration of central apneic events and the frequency of accompanying arousals during nonrapid and rapid eye movement (NREM and REM, respectively) sleep across the light/dark cycle. Electroencephalography, electromyography, core body temperature, and activity were recorded for 24 h following implantation of telemeters in wild-type (Tph2+/+) and tryptophan hydroxylase 2 knockout (Tph2-/-) male mice. The frequency and duration of central apneic events were increased, the number of apneic events coupled to an arousal was decreased, and the ventilatory sensitivity to hypoxia and hypercapnia was decreased in the Tph2-/- compared with the Tph2+/+ mice during NREM sleep. Apnea frequency and duration were similar in the Tph2-/- and Tph2+/+ mice during REM sleep. The duration of apneic events during REM compared with NREM sleep was similar in the Tph2-/- mice. In contrast, the duration was greater during REM sleep in the Tph2+/+ mice. Our results also revealed that apnea frequency was greater during the light compared with the dark cycle. Circadian modulation of this variable was evident in both the Tph2-/- and Tph2+/+ mice during NREM and REM sleep. We conclude that depletion of 5-HT increases the frequency and duration of central apneic events, dampens arousal, and blunts the ventilatory response to hypoxia and hypercapnia during NREM sleep but is not essential for the circadian modulation of these variables. NEW & NOTEWORTHY The presence of serotonin (5-HT) in the central nervous system diminishes the frequency of central apneic events. This neuromodulator also moderates the duration of central apneic events and promotes arousal from central events if they occur during nonrapid eye movement (NREM) sleep. However, 5-HT is not responsible for the circadian modulation of apnea frequency, which we found was greater during NREM sleep in the light compared with the dark cycle.
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PMID:Genetic depletion of 5-HT increases central apnea frequency and duration and dampens arousal but does not impact the circadian modulation of these variables. 3033 78